ACYLOXYALKYL CARBAMATE PRODRUGS, METHODS OF SYNTHESIS AND USE

FIELD

The disclosure relates to acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof, methods of making acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof, methods of using acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof, and pharmaceutical compositions comprising acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof to treat disease. The disclosure also relates to acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof suitable for oral administration and sustained release dosage forms.

BACKGROUND

(±)-4-Amino-3-(4-chlorophenyl)butanoic acid (baclofen), (1), is an analog of gamma-aminobutyric acid (i.e., GABA) that selectively activates GABA_Breceptors, resulting in neuronal hyperpolarization. GABA_Breceptors are located in laminae I-IV of the spinal cord, where primary sensory fibers end. These G-protein coupled receptors activate conductance by K⁺-selective ion channels and may reduce currents mediated by Ca²⁺ channels in certain neurons. Baclofen has a presynaptic inhibitory effect on the release of excitatory neurotransmitters and also acts postsynaptically to decrease motor neuron firing (see Bowery, Trends Pharmacol. Sci. 1989, 10, 401-407; Misgeld et al., Prog. Neurobiol. 1995, 46, 423-462).

Many examples of compounds having antagonistic activity at GABA_Breceptors exist and block the effects of baclofen in vitro and in vivo. Examples of GABA_Bantagonists include certain aminophosphonic acids (e.g. phaclofen), aminosulfonic acids (e.g. saclofen and 2-hydroxysaclofen), and aminophosphinic acids, particularly certain 3-aminopropylphosphinic acids.

Certain 3-aminopropylphosphinic acid analog GABA_Bantagonists are described in Froestl et al., J. Med. Chem. 1995, 38, 3313-3331; Dingwall et al., Tetrahedron 1989, 45, 3787-3808; Deprele and Montchamp, J. Org. Chem. 2001, 66, 6745-6755; Dingwall et al., U.S. Pat. No. 4,656,298; Baylis et al., U.S. Pat. No. 5,013,863; Baylis et al., U.S. Pat. No. 5,051,524; Baylis et al., U.S. Pat. No. 5,300,679; Marescaux et al., U.S. Pat. No. 5,229,379; Marescaux et al., U.S. Pat. No. 5,407,922; Mickel et al., U.S. Pat. No. 5,332,729; Mickel, U.S. Pat. No. 5,376,684; and Mickel et al., U.S. Pat. No. 5,424,441. Examples of aminopropylphosphinic analog GABA_Bantagonists include:

3-Aminopropyl(n-butyl)phosphinic acid;
3-Aminopropyl(diethoxymethyl)phosphinic acid;
3-Aminopropyl(benzyl)phosphinic acid;
3-Amino-2(S)-hydroxypropyl(benzyl)phosphinic acid;
3-Amino-2-hydroxypropyl(cyclohexylmethyl)phosphinic acid;
3-Amino-2(S)-hydroxypropyl(cyclohexylmethyl)phosphinic acid;
3-(4-Chlorobenzylamino)-2(R)-hydroxypropyl(benzyl)phosphinic acid;
3-(4-Chlorobenzylamino)propyl(diethoxymethyl)phosphinic acid;
3-(4-Chlorobenzylamino)-2-hydroxypropyl(n-butyl)phosphinic acid;
3-(3,4-Dichlorobenzylamino)-2(S)-hydroxypropyl(benzyl)phosphinic acid;
3-(3,4-Dichlorobenzylamino)-2(S)-hydroxypropyl(diethoxymethyl)phosphinic acid;
3-(4-Chlorobenzylamino)propyl(cyclohexylmethyl)phosphinic acid;
3-{N-[1-(3,4-Dichlorophenyl)ethyl]amino}-2-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1-(3,4-Dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1-(3,4-Dichlorophenyl)ethyl]amino}-2(R)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1 (R)-(3,4-Dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1(S)-(3,4-Dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1 (R)-(3,4-Dichlorophenyl)ethyl]amino}-2(R)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1(S)-(3,4-Dichlorophenyl)ethyl]amino}-2(R)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1-(3,4-Dichlorophenyl)ethyl]amino}-2-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1-(3,4-Dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1-(3,4-Dichlorophenyl)ethyl]amino}-2(R)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1 (R)-(3,4-Dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1(S)-(3,4-Dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1(R)-(3,4-Dichlorophenyl)ethyl]amino}-2(R)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1(S)-(3,4-Dichlorophenyl)ethyl]amino}-2(R)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1-(3-Carboxyphenyl)ethyl]amino}-2-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1-(3-Carboxyphenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1-(3-Carboxyphenyl)ethyl]amino}-2(R)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1 (R)-(3-Carboxyphenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1(S)-(3-Carboxyphenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1 (R)-(3-Carboxyphenyl)ethyl]amino}-2(R)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1(S)-(3-carboxyphenyl)ethyl]amino}-2(R)-hydroxy-propyl-(cyclohexylmethyl)-phosphinic acid;
3-{N-[1-(3-Carboxyphenyl)ethyl]amino}-2-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1-(3-Carboxyphenyl)ethyl]amino}-2(S)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1-(3-Carboxyphenyl)ethyl]amino}-2(R)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1 (R)-(3-Carboxyphenyl)ethyl]amino}-2(S)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1(S)-(3-Carboxyphenyl)ethyl]amino}-2(S)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1 (R)-(3-Carboxyphenyl)ethyl]amino}-2(R)-hydroxy-propyl-(benzyl)-phosphinic acid;
3-{N-[1(S)-(3-Carboxyphenyl)ethyl]amino}-2(R)-hydroxy-propyl-(benzyl)-phosphinic acid;

pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable solvates of any of the foregoing.

GABA_Bantagonists are useful in the treatment of cognitive or memory disorders including Mild Cognitive Impairment (MCI) and cognitive impairment associated with Alzheimer's disease (see e.g., Baylis et al., U.S. Pat. No. 5,190,933; Pearlman et al., U.S. Application Publication No. 2002/0187977; Froestl et al., Biochem. Pharmacol. 2004, 68, 1479-1487; Helm et al., Neuropharmacol. 2005, 48, 956-964; Mondadori et al., Behav. Brain Res. 1996, 77, 227-229; Mondadori et al., Behav. Neural Biol. 1993, 60, 62-68; and Nakagawa et al., Brain Res. 1997, 766, 101-106).

GABA_Bantagonists are also useful in the treatment of depressive moods or anxiety states (see e.g., Slattery et al., J. Pharmacol. Exp. Ther. 2005, 312, 290-296; and Nakagawa et al., Eur. J. Pharmacol. 1999, 381, 1-7).

GABA_Bantagonists are also useful in the treatment of epilepsy, particularly “petit-mal” type epilepsy, including spontaneous absence epilepsy and atypical absence epilepsy (see e.g., Marescaux et al., U.S. Pat. No. 5,407,922; Marescaux et al., U.S. Pat. No. 5,545,631; Czuczwar and Patsalos, CNS Drugs, 2001, 15, 339-350; Getova et al., Eur. J. Pharmacol. 1997, 320, 9-13; Vergnes et al., Eur. J. Pharmacol. 1997, 332, 245-255; and Marescaux et al., J. Neural Transm. 1992, 35, 179-188).

Typical ligands for GABA_Breceptors such as baclofen and the zwitterionic 3-aminopropylphosphinic acids noted above are polar molecules that lack the requisite physicochemical characteristics for effective passive permeability across cellular membranes. For baclofen, passage of the drug across the gastrointestinal (GI) tract and the blood-brain barrier (BBB) is mediated primarily by active transport processes rather than by passive diffusion. Accordingly, baclofen is a substrate for active transport mechanisms shared by neutral α-amino acids such as leucine and β-amino acids such as β-alanine and taurine (van Bree et al., Pharm. Res. 1988, 5, 369-371; Cercos-Fortea et al., Biopharm. Drug. Disp. 1995, 16, 563-577; Deguchi et al., Pharm. Res. 1995, 12, 1838-1844; Moll-Navarro et al., J. Pharm. Sci. 1996, 85, 1248-1254). 3-Aminopropylphosphinic acids are also likely to exploit related active transport mechanisms to permeate the GI mucosa following oral administration.

Another common feature shared by baclofen and 3-aminopropylphosphinic acid GABA_Breceptor antagonists is their rapid clearance from the systemic circulation, which leads to the necessity for frequent dosing in humans (e.g. three or four times daily) (see Bowery, supra; “Commercial and Pipeline Perspectives: Upper GI Disorders”, Data Monitor Report, September 2004, p. 147; Gleiter et al., J. Clin. Pharm. 1996, 36, 428-438; and Froestl et al., Biochem. Pharmacol. 2004, 68, 1479-1487). Sustained release oral dosage formulations are a conventional solution to the problem of rapid systemic drug clearance, as is well known in the art (see e.g., “Remington's Pharmaceutical Sciences,” Philadelphia College of Pharmacy and Science, 19th Edition, 1995). Osmotic delivery systems are also recognized methods for sustained drug delivery (see e.g., Verma et al., Drug Dev. Ind. Pharm. 2000, 26, 695-708). Successful application of these technologies depends on the drug of interest having an effective level of absorption from the large intestine (also referred to herein as the colon), where the dosage form spends a majority of its time during its passage down the gastrointestinal tract. Baclofen, and likely other zwitterionic GABA_Breceptor ligands, is poorly absorbed following administration into the colon in animal models (Merino et al., Biopharm. Drug. Disp. 1989, 10, 279-297), presumably because the transporter proteins mediating baclofen absorption in the upper region of the small intestine are not expressed in the large intestine. Development of an oral controlled release formulation for zwitterionic GABA_Breceptor antagonists should considerably improve the convenience, efficacy, and side effect profile of GABA_Bantagonist therapy. However, the rapid passage of conventional dosage forms through the proximal absorptive region of the small intestine has thus far prevented the successful application of sustained release technologies to these drugs. A number of exploratory delivery technologies that rely on either mucoadhesion or gastric retention have been suggested to achieve sustained delivery of baclofen (Sinnreich, U.S. Pat. No. 4,996,058; Khanna, U.S. Pat. No. 5,091,184; Fara et al., supra; Dudhara et al., International Publication No. WO 03/011255) though to date none of these appear to be able to achieve sustained blood levels of baclofen in human subjects. More recently, acyloxyalkyl carbamate prodrugs of baclofen and analogs thereof have been shown to provide enhanced bioavailability of baclofen following oral administration as described in co-pending application Gallop et al., International Publication No. WO 2005/019163 entitled “Acyloxyalkyl Carbamate Prodrugs, Methods, Synthesis and Use,” filed Aug. 20, 2004. Thus, there is a need for new prodrugs of 3-aminopropylphosphinic acid GABA_Breceptor antagonists, which are well absorbed in the large intestine/colon and hence are suitable for oral sustained release formulations, thus improving the convenience, efficacy, and side effect profile of GABA_Bantagonist therapy.

SUMMARY

These and other needs are satisfied by the disclosure herein of acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof, pharmaceutical compositions of acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof, methods of making acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof, and methods of using acyloxyalkyl carbamate prodrugs of 3-aminopropylphosphinic acid and analogs thereof and/or pharmaceutical compositions thereof to treat various medical disorders.

In a first aspect, a compound of Formula (I) is provided:

pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of any of the foregoing, wherein:

R¹is chosen from acyl, substituted acyl, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl;

R²and R³is chosen from hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl, or R²and R³together with the carbon atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, or substituted cycloheteroalkyl ring;

R⁴is chosen from C_2-6alkyl, substituted C_2-6alkyl, benzyl, substituted benzyl, C_4-7cycloalkyl, C_3-7cycloalkylmethyl, and dialkoxymethyl;

R⁵is chosen from hydrogen, hydroxy, mercapto, fluoro, oxo, C_1-4alkyl, substituted C_1-4alkyl, aryl, substituted aryl, C_3-6cycloalkyl, substituted C_3-6cycloalkyl, heteroaryl, substituted heteroaryl, C_7-9phenylalkyl, and substituted C_7-9phenylalkyl;

R⁶and R⁷is chosen from hydrogen, C_1-6alkyl, C_1-6alkoxy, aryl, substituted aryl, C_3-6cycloalkyl, heteroaryl, substituted heteroaryl, C_7-9phenylalkyl, and substituted C_7-9phenylalkyl; and

R⁸is chosen from hydrogen, C_1-6alkyl, substituted C_1-6alkyl, aryl, substituted aryl, C_3-6cycloalkyl, substituted C_3-6cycloalkyl, heteroaryl, substituted heteroaryl, C_7-9phenylalkyl, and substituted C_7-9phenylalkyl.

In a second aspect, pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, and a pharmaceutically acceptable vehicle such as a diluent, carrier, excipient, or adjuvant are provided. The choice of diluent, carrier, excipient, or adjuvant will depend upon, among other factors, the desired mode of administration.

In a third aspect, methods are provided for treating cognitive or memory disorders such as mild cognitive impairment and cognitive impairment associated with Alzheimer's disease, mood disorders such as depression and anxiety, and movement disorders such as epilepsy. The methods generally involve administering to a patient in need of such treatment a therapeutically effective amount of a compound of Formula (I) and/or a pharmaceutical composition comprising a compound of Formula (I).

In a fourth aspect, a method of maintaining a therapeutically effective concentration of a 3-aminopropylphosphinic acid analog in the blood plasma of a patient for a time period chosen from at least about 4 hours, at least about 8 hours, and at least about 12 hours, comprising orally administering a pharmaceutical composition comprising the corresponding compound of Formula (I) to the patient is provided.

DETAILED DESCRIPTION
Definitions

A dash (“-”) that is not between two letters or symbols is used to indicate a point of attachment for a moiety or substituent. For example, —CONH₂is a moiety bonded through the carbon atom.

“1-Acyloxy-Alkyl Carbamate” refers to an N-1-acyloxy-alkoxycarbonyl derivative of a 3-aminopropylphosphinic acid analog as encompassed by compounds of Formula (I) disclosed herein.

“Alkyl,” by itself or as part of another substituent, refers to a saturated or unsaturated, branched or straight-chain monovalent hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane, alkene or alkyne. Examples of alkyl groups include, but are not limited to, methyl; ethyls such as ethanyl, ethenyl, and ethynyl; propyls such as propan-1-yl, propan-2-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl (allyl), prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl, but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc.; and the like.

The term “alkyl” is specifically intended to include groups having any degree or level of saturation, i.e., groups having exclusively single carbon-carbon bonds, groups having one or more double carbon-carbon bonds, groups having one or more triple carbon-carbon bonds, and groups having mixtures of single, double, and triple carbon-carbon bonds. Where a specific level of saturation is intended, the expressions “alkanyl,” “alkenyl,” and “alkynyl” are used. In certain embodiments, alkyl groups comprise from 1 to 20 carbon atoms, in certain embodiments, from 1 to 10 carbon atoms, and in certain embodiments, from 1 to 6 carbon atoms.

“Alkanyl,” by itself or as part of another substituent, refers to a saturated, branched or straight-chain alkyl radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane. Examples of alkanyl groups include, but are not limited to, methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl (isopropyl), etc.; butanyls such as butan-1-yl, butan-2-yl (sec-butyl),

“Alkenyl,” by itself or as part of another substituent, refers to an unsaturated, branched or straight-chain alkyl radical having at least one carbon-carbon double bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkene. The group may be in either the cis or trans conformation about each double bond. Examples of alkenyl groups include, but are not limited to, ethenyl; propenyls such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl (allyl), prop-2-en-2-yl, butenyls such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, etc.; and the like.

“Alkynyl,” by itself or as part of another substituent, refers to an unsaturated, branched or straight-chain alkyl radical having at least one carbon-carbon triple bond derived by the removal of one hydrogen atom from a single carbon atom of a parent alkyne. Examples of alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butynyls such as but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc.; and the like.

“Acyl” by itself or as part of another substituent refers to the radical —C(O)R³⁰, where R³⁰is chosen from hydrogen, alkyl, cycloalkyl, cycloheteroalkyl, aryl, arylalkyl, heteroalkyl, heteroaryl, and heteroarylalkyl as defined herein. Examples of acyl groups include, but are not limited to, formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl, benzylcarbonyl, and the like.

“Alkoxy,” by itself or as part of another substituent, refers to the radical —OR³¹where R³¹represents an alkyl or cycloalkyl group as defined herein. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, cyclohexyloxy, and the like.

“Alkoxycarbonyl,” by itself or as part of another substituent, refers to the radical —C(O)OR³²where R³²represents an alkyl or cycloalkyl group as defined herein. Examples of alkoxycarbonyl groups include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, cyclohexyloxycarbonyl, and the like.

“Alkylamino,” by itself or as part of another substituent, refers to the radical —NHR³¹where R³¹is chosen from alkyl and cycloalkyl, as defined herein.

“3-Aminopropylphosphinic acid analog” refers to a compound of Formula (II):

wherein R⁴is chosen from C_2-6alkyl, substituted C_2-6alkyl, benzyl, substituted benzyl, C_4-7cycloalkyl, C_3-7cycloalkylmethyl, and dialkoxymethyl;

R⁶and R⁷is chosen from hydrogen, C_1-6alkyl, C_1-6alkoxy, aryl, substituted aryl, C_3-6cycloalkyl, heteroaryl, substituted heteroaryl, C_7-9phenylalkyl, and substituted C_7-9phenylalkyl; and

In certain embodiments of compounds of Formula (II), each of the one or more substituent groups is independently chosen from halogen, C_1-3alkyl, —OH, —NH₂, —SH, —COOH, C_1-3alkoxy, C_1-3acyl, C_1-3thioalkyl, C_1-3alkoxycarbonyl, C_1-3alkylamino, and C_1-3dialkylamino.

Within the scope of this disclosure, it is to be understood that when R⁵is an oxo group the bond between R⁵and the carbon to which it is bonded is a double bond.

“Aryl,” by itself or as part of another substituent, refers to a monovalent aromatic hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of a parent aromatic ring system. Aryl encompasses 5- and 6-membered carbocyclic aromatic rings, for example, benzene; bicyclic ring systems wherein at least one ring is carbocyclic and aromatic, for example, naphthalene, indane, and tetralin; and tricyclic ring systems wherein at least one ring is carbocyclic and aromatic, for example, fluorene. Aryl encompasses multiple ring systems having at least one carbocyclic aromatic ring fused to at least one carbocylic aromatic ring, cycloalkyl ring, or heterocycloalkyl ring. For example, aryl includes 5- and 6-membered carbocyclic aromatic rings fused to a 5- to 7-membered heterocycloalkyl ring containing one or more heteroatoms chosen from N, O, and S. For such fused, bicyclic ring systems wherein only one of the rings is a carbocyclic aromatic ring, the point of attachment may be at the carbocyclic aromatic ring or the heterocycloalkyl ring. Examples of aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexylene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene, and the like. In certain embodiments, aryl groups have from 5 to 20 carbon atoms, and in certain embodiments, from 5 to 12 carbon atoms. In certain embodiments, aryl has from 6 to 10 carbon atoms.

“Arylalkyl,” by itself or as part of another substituent, refers to an acyclic alkyl radical in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp³carbon atom, is replaced with an aryl group. Examples of arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl, 2-naphthylethen-1-yl, naphthobenzyl, 2-naphthophenylethan-1-yl, and the like. Where specific alkyl moieties are intended, the nomenclature arylalkanyl, arylalkenyl, and/or arylalkynyl is used. In certain embodiments, an arylalkyl group is (C₇-C₃₀) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C₁-C₁₀) and the aryl moiety is (C₆-C₂₀), and in certain embodiments, an arylalkyl group is (C₇-C₂₀) arylalkyl, e.g., the alkanyl, alkenyl, or alkynyl moiety of the arylalkyl group is (C₁-C₈) and the aryl moiety is (C₆-C₂).

“AUC” is the area under a curve representing the concentration of a compound or metabolite thereof in a biological fluid in a patient as a function of time following administration of the compound to the patient. In certain embodiments, the compound is a prodrug and the metabolite is a drug. Examples of biological fluids include plasma and blood. The AUC may be determined by measuring the concentration of a compound or metabolite thereof in a biological fluid such as the plasma or blood using methods such as liquid chromatography-tandem mass spectrometry (LC/MS/MS), at various time intervals, and calculating the area under the plasma concentration-versus-time curve. Suitable methods for calculating the AUC from a drug concentration-versus-time curve are well known in the art. For example, an AUC for an α-amino acid may be determined by measuring the concentration of the α-amino acid in the plasma or blood of a patient following administration of a compound of Formula (I) to the patient.

“C_max” is the maximum concentration of a drug in the plasma or blood of a patient following administration of a dose of the drug or prodrug to the patient.

“Compounds” of Formula (I) disclosed herein include any specific compounds within the formula whose structure is disclosed herein. Compounds may be identified by their chemical structure and/or chemical name. If the chemical structure and chemical name conflict, the chemical structure is determinative of the identity of the compound.

The compounds described herein may comprise one or more chiral centers and/or double bonds and therefore may exist as stereoisomers such as double-bond isomers (i.e., geometric isomers), enantiomers, and diastereomers. Accordingly, any chemical structures within the scope of the specification depicted, in whole or in part, with a relative configuration encompass all possible enantiomers and stereoisomers of the illustrated compounds including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures may be resolved into their component enantiomers or stereoisomers using separation techniques and stereoisomerically pure forms may be synthesized using chiral synthesis techniques well known to the skilled artisan.

Compounds of Formula (I) include, but are not limited to, optical isomers of compounds of Formula (I), racemates thereof, and other mixtures thereof. In such embodiments, the single enantiomers or diastereomers, i.e., optically active forms may be obtained by asymmetric synthesis or by resolution of the racemates. Resolution of the racemates may be accomplished, for example, by conventional methods such as crystallization in the presence of a resolving agent, or chromatography, using, for example a chiral high-pressure liquid chromatography (HPLC) column. In addition, compounds of Formula (I) include Z- and E-forms (or cis- and trans-forms) of compounds with double bonds. In embodiments in which compounds of Formula (I) exist in various tautomeric forms, compounds of Formula (I) include any and all tautomeric forms of the compound.

The compounds of Formula (I) may also exist in several tautomeric forms including the enol form, the keto form, and mixtures thereof. Accordingly, the chemical structures depicted herein encompass any and all possible tautomeric forms of the illustrated compounds. The compounds of Formula (I) also include isotopically labeled compounds where one or more atoms have an atomic mass different from the atomic mass conventionally found in nature. Examples of isotopes that may be incorporated into the compounds disclosed herein include, but are not limited to, ²H, ³H, ¹¹C, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, etc. Compounds may exist in unsolvated forms as well as solvated forms, including hydrated forms and as N-oxides. In general, compounds may be hydrates, solvates, or N-oxides. Certain compounds may exist in multiple crystalline or amorphous forms. Compounds of Formula (I) include pharmaceutically acceptable salts thereof, pharmaceutically acceptable solvates of the free acid form of any of the foregoing, as well as crystalline forms of any of the foregoing.

In general, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present disclosure. Further, it should be understood, when partial structures of the compounds are illustrated, that an asterisk indicates the point of attachment of the partial structure to the rest of the molecule.

“Corresponding 3-aminopropylphosphinic acid analog” refers to a compound of Formula (II) having the same R⁴, R⁵, R⁶, R⁷, and R⁸groups as the acyloxyalkyl carbamate prodrug of the 3-aminopropylphosphinic acid analog of Formula (I). The “corresponding acyloxyalkyl carbamate prodrug” refers to the compound of Formula (I) having the same R⁴, R⁵, R⁶, R⁷, and R⁸groups as the 3-aminopropylphosphinic acid analog of Formula (II)

“Cycloalkoxycarbonyl,” by itself or as part of another substituent, refers to the radical —C(O)OR³⁶where R³⁶represents an cycloalkyl group as defined herein. Examples of cycloalkoxycarbonyl groups include, but are not limited to, cyclobutyloxycarbonyl, cyclohexyloxycarbonyl, and the like.

“Cycloalkyl,” by itself or as part of another substituent, refers to a saturated or partially unsaturated cyclic alkyl radical. Where a specific level of saturation is intended, the nomenclature “cycloalkanyl” or “cycloalkenyl” is used. Examples of cycloalkyl groups include, but are not limited to, groups derived from cyclopropane, cyclobutane, cyclopentane, cyclohexane, and the like. In certain embodiments, the cycloalkyl group is C_3-10cycloalkyl, and in certain embodiments C_3-7cycloalkyl.

“Cycloheteroalkyl,” by itself or as part of another substituent, refers to a saturated or partially unsaturated cyclic alkyl radical in which one or more carbon atoms (and any associated hydrogen atoms) is replaced with the same or different heteroatom. Examples heteroatoms to replace the carbon atom(s) include, but are not limited to, N, P, O, S, Si, etc. Where a specific level of saturation is intended, the nomenclature “cycloheteroalkanyl” or “cycloheteroalkenyl” is used. Examples of cycloheteroalkyl groups include, but are not limited to, groups derived from epoxides, azirines, thiiranes, imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, and the like.

“Dialkylamino” by itself or as part of another substituent refers to the radical —NR⁴³R⁴⁴where R⁴³and R⁴⁴are independently chosen from alkyl, cycloalkyl, cycloheteroalkyl, arylalkyl, heteroalkyl, and heteroarylalkyl, or R⁴³and R⁴⁴together with the nitrogen to which they are bonded form a cycloheteroalkyl ring.

“Halogen” refers to a fluoro, chloro, bromo, or iodo group.

“Heteroalkyl, heteroalkanyl, heteroalkenyl, and heteroalkynyl,” by themselves or as part of another substituent, refer to alkyl, alkanyl, alkenyl, and alkynyl groups, respectively, in which one or more of the carbon atoms (and any associated hydrogen atoms) is replaced with the same or different heteroatomic groups. Typical heteroatomic groups which may be included in these groups include, but are not limited to, —O—, —S—, —O—O—, —S—S—, —O—S—, —NR³⁷R³⁸—, ═N—N═, —N═N—, —N═N—NR³⁹R⁴⁰, —PR⁴¹—, —P(O)₂—, —POR⁴²—, —O—P(O)₂—, —SO—, —SO₂—, —SnR⁴³R⁴⁴— and the like, where R³⁷, R³⁸, R³⁹, R⁴⁰, R⁴¹R⁴², and R⁴⁴is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl.

“Heteroaryl,” by itself or as part of another substituent, refers to a monovalent heteroaromatic radical derived by the removal of one hydrogen atom from a single atom of a parent heteroaromatic ring system. Heteroaryl encompasses multiple ring systems having at least one heteroaromatic ring fused to at least one other ring, which may be aromatic or non-aromatic. Heteroaryl encompasses 5- to 7-membered aromatic, monocyclic rings containing one or more, for example, from 1 to 4, or in certain embodiments, from 1 to 3, heteroatoms chosen from N, O, and S, with the remaining ring atoms being carbon; and bicyclic heterocycloalkyl rings containing one or more, for example, from 1 to 4, or in certain embodiments, from 1 to 3, heteroatoms chosen from N, O, and S, with the remaining ring atoms being carbon and wherein at least one heteroatom is present in an aromatic ring. For example, heteroaryl includes a 5- to 7-membered heteroaromatic ring fused to a 5- to 7-membered cycloalkyl ring. For such fused, bicyclic heteroaryl ring systems wherein only one of the rings contains one or more heteroatoms, the point of attachment may be at the heteroaromatic ring or the cycloalkyl ring. In certain embodiments, when the total number of N, S, and O atoms in the heteroaryl group exceeds one, the heteroatoms are not adjacent to one another. In certain embodiments, the total number of N, S, and O atoms in the heteroaryl group is not more than two. In certain embodiments, the total number of N, S, and O atoms in the aromatic heterocycle is not more than one. Heteroaryl does not encompass or overlap with aryl as defined herein.

Examples of heteroaryl groups include, but are not limited to, groups derived from acridine, arsindole, carbazole, β-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like. In certain embodiments, a heteroaryl group is a 5- to 20-membered heteroaryl, and in certain embodiments a 5- to 10-membered heteroaryl. In certain embodiments, heteroaryl groups are those derived from thiophene, pyrrole, benzothiophene, benzofuran, indole, pyridine, quinoline, imidazole, oxazole, and pyrazine.

“Heteroarylalkyl,” by itself or as part of another substituent, refers to an acyclic alkyl radical in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or Sp³carbon atom, is replaced with a heteroaryl group. Where specific alkyl moieties are intended, the nomenclature heteroarylalkanyl, heteroarylalkenyl, and heterorylalkynyl is used. In certain embodiments, the heteroarylalkyl group is a 6-30 membered heteroarylalkyl, e.g., the alkanyl, alkenyl, or alkynyl moiety of the heteroarylalkyl is 1-10 membered and the heteroaryl moiety is a 5-20-membered heteroaryl, and in certain embodiments, 6-20 membered heteroarylalkyl, e.g., the alkanyl, alkenyl, or alkynyl moiety of the heteroarylalkyl is 1-8 membered and the heteroaryl moiety is a 5-12-membered heteroaryl.

“Parent Aromatic Ring System” refers to an unsaturated cyclic or polycyclic ring system having a conjugated π (pi) electron system. Specifically included within the definition of “parent aromatic ring system” are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, for example, fluorene, indane, indene, phenalene, etc. Typical parent aromatic ring systems include, but are not limited to, aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexylene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene, and the like.

“Parent Heteroaromatic Ring System” refers to a parent aromatic ring system in which one or more carbon atoms (and any associated hydrogen atoms) is replaced with the same or different heteroatom. Typical heteroatoms to replace the carbon atoms include, but are not limited to, N, P, O, S, Si, etc. Specifically included within the definition of “parent heteroaromatic ring systems” are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, arsindole, benzodioxan, benzofuran, chromane, chromene, indole, indoline, xanthene, etc. Typical parent heteroaromatic ring systems include, but are not limited to, arsindole, carbazole, β-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like.

“Patient” includes mammals, such as for example, humans.

“Pharmaceutical composition” refers to at least one compound of Formula (I) and at least one pharmaceutically acceptable vehicle with which the compound is to be administered to a patient.

“Pharmaceutically acceptable salt” refers to a salt of a compound, which possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; and (2) salts formed when an acidic proton present in the parent compound is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth metal ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, and the like.

“Pharmaceutically acceptable vehicle” refers to a pharmaceutically acceptable diluent, a pharmaceutically acceptable adjuvant, a pharmaceutically acceptable excipient, a pharmaceutically acceptable carrier, or a combination of any of the foregoing with which the compound of Formula (I) may be administered to a patient and which does not destroy the pharmacological activity thereof, and which is nontoxic when administered in doses sufficient to provide a therapeutically effective amount of the compound.

“Pharmaceutically acceptable” refers to approved or approvable by a regulatory agency of a federal or a state government, listed in the U.S. Pharmacopoeia, or listed other generally recognized pharmacopoeia for use in mammals, including humans.

“Prodrug” refers to a derivative of an active compound (drug) that undergoes a transformation under the conditions of use, such as within the body, to release an active drug. Prodrugs are frequently, but not necessarily, pharmacologically inactive until converted into the active drug. Prodrugs may be obtained by bonding a promoiety (defined herein), typically via a functional group, to a drug.

“Promoiety” refers to a group bonded to a drug, typically to a functional group of the drug, via bond(s) that are cleavable under specified conditions of use. The bond(s) between the drug and promoiety may be cleaved by enzymatic or non-enzymatic means. Under the conditions of use, for example following administration to a patient, the bond(s) between the drug and promoiety may be cleaved to release the parent drug. The cleavage of the promoiety may proceed spontaneously, such as via a hydrolysis reaction, or it may be catalyzed or induced by another agent, such as by an enzyme, by light, by acid, or by a change of or exposure to a physical or environmental parameter, such as a change of temperature, pH, etc. The agent may be endogenous to the conditions of use, such as an enzyme present in the systemic circulation to which the prodrug is administered or the acidic conditions of the stomach, or the agent may be supplied exogenously. In certain embodiments, the drug is 3-aminopropylphosphinic acid or analog thereof of Formula (II) and the promoiety is an acyloxyalkyloxycarbonyl group having the structure:

where R¹, R², and R³are defined herein.

“Protecting group” refers to a group of atoms, which when attached to a reactive functional group in a molecule, masks, reduces, or prevents reactivity of the functional group. Examples of protecting groups can be found in Green et al., “Protective Groups in Organic Chemistry,” (Wiley, 2^nded. 1991) and Harrison et al., “Compendium of Synthetic Organic Methods,” Vols. 1-8 (John Wiley and Sons, 1971-1996). Representative amino protecting groups include, but are not limited to, formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl (CBZ), tert-butoxycarbonyl (Boc), trimethylsilyl (TMS), 2-trimethylsilyl-ethanesulfonyl (SES), trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (FMOC), nitro-veratryloxycarbonyl (NVOC), and the like. Representative hydroxy protecting groups include, but are not limited to, those where the hydroxy group is either acylated or alkylated such as benzyl, and trityl ethers as well as alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers, and allyl ethers.

“Pharmaceutically acceptable solvate” refers to a molecular complex of a compound with one or more solvent molecules in a stoichiometric or non-stoichiometric amount. Such solvent molecules are those commonly used in the pharmaceutical arts, e.g., water, ethanol, and the like. A molecular complex of a compound or moiety of a compound and a solvent can be stabilized by non-covalent intra-molecular forces such as, electrostatic forces, van der Waals forces, and hydrogen bonds. The term “hydrate” refers to a complex in which the one or more solvent molecules are water including monohydrates and hemi-hydrates.

“Substantially one diastereomer” refers to a compound containing 2 or more stereogenic centers such that the diastereomeric excess (d.e.) of the compound is greater than or equal to 90%. In some embodiments, the d.e. is, for example, greater than or equal to 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and 99%.

“Substituted” refers to a group in which one or more hydrogen atoms are independently replaced with the same or different substituent(s). Examples of substituents include, but are not limited to, —X, —R⁶⁰, —O⁻, ═O, —OR⁶⁰, —SR⁶⁰, —S⁻, ═S, —NR⁶⁰R⁶¹, ═NR⁶⁰, —CX₃, —CN, —CF₃, —OCN, —SCN, —NO, —NO₂, ═N₂, —N₃, —S(O)₂O⁻, —S(O)₂OH, —S(O)₂R⁶⁰, —OS(O₂)O⁻, —OS(O)₂R⁶⁰, —P(O)(O⁻)₂, —P(O)(OR⁶⁰)(O⁻), —OP(O)(OR⁶⁰)(OR⁶¹), —C(O)R⁶⁰, —C(S)R⁶⁰, —C(O)OR⁶⁰, —C(O)NR⁶⁰R⁶¹, —C(O)O⁻, —(S)OR⁶⁰, —NR⁶²C(O)NR⁶⁰R⁶¹, —NR⁶²C(S)NR⁶⁰R⁶¹, —NR⁶²C(NR⁶³)NR⁶⁰R⁶¹, —C(NR⁶²)NR⁶⁰OR⁶¹, —S(O)₂, NR⁶⁰R⁶¹, —NR⁶³S(O)₂R⁶⁰, —NR⁶³C(O)R¹⁰, and —S(O)R⁶⁰where each X is independently a halogen; each R⁶⁰and R⁶¹are independently chosen from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, and substituted heteroarylalkyl, or R⁶⁰and R⁶¹, together with the nitrogen atom to which they are bonded, form a cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, or substituted heteroaryl ring; and each R⁶²and R⁶³are independently chosen from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl, or R⁶²and R⁶³, together with the atom to which they are bonded, form one or more cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, or substituted heteroaryl rings. In certain embodiments, a tertiary amine or aromatic nitrogen may be substituted with one or more oxygen atoms to form the corresponding nitrogen oxide.

In certain embodiments of the compounds of Formula (I) and Formula (II), each of the one or more substituent groups is independently chosen from halogen, C_1-3alkyl, —OH, —NH₂, —SH, —COOH, C_1-3alkoxy, C_1-3acyl, C_1-3thioalkyl, C_1-3alkoxycarbonyl, C_1-3alkylamino, and C_1-3dialkylamino.

“Thioalkyl,” by itself or as part of another substituent, refers to the radical —SR⁴¹where R⁴¹is alkyl as defined herein. “Mercapto,” by itself or as part of another substituent, refers to the radical —SR⁴¹where R⁴¹is hydrogen.

“Treating” or “treatment” of a disease refers to arresting or ameliorating a disease, disorder, or at least one of the clinical symptoms of a disease or disorder. In certain embodiments, “treating” or “treatment” refers to arresting or ameliorating at least one physical parameter of the disease or disorder, which may or may not be discernible by the patient. In certain embodiments, “treating” or “treatment” refers to inhibiting or controlling the disease or disorder, either physically (e.g., stabilization of a discernible symptom), physiologically (e.g., stabilization of a physical parameter), or both. In certain embodiments, “treating” or “treatment” refers to delaying, in some cases indefinitely, the onset of a disease or disorder.

“Therapeutically effective amount” refers to the amount of a compound that, when administered to a subject for treating a disease, or disorder, or at least one of the clinical symptoms of a disease or disorder, is sufficient to affect such treatment of the disease, disorder, or symptom. The “therapeutically effective amount” may vary depending, for example, on the compound, the disease, disorder, and/or symptoms of the disease, severity of the disease, disorder, and/or symptoms of the disease, the age, weight, and/or health of the patient to be treated, and the judgment of the prescribing physician. An appropriate amount in any given instance may be readily ascertained by those skilled in the art or capable of determination by routine experimentation.

Reference is now be made in detail to certain embodiments of compounds and methods of the present disclosure. The disclosed embodiments are not intended to be limiting of the claims. To the contrary, the claims are intended to cover all alternatives, modifications, and equivalents.

Compounds

In a first aspect, compounds of Formula (I) are provided:

and pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable solvates of any of the foregoing, wherein:

R⁴is chosen from C_2-6alkyl, substituted C_2-6alkyl, benzyl, substituted benzyl, C_4-7cycloalkyl, C_3-7cycloalkylmethyl, and dialkoxymethyl;

R⁶and R⁷is chosen from hydrogen, C_1-6alkyl, C_1-6alkoxy, aryl, substituted aryl, C_3-6cycloalkyl, heteroaryl, substituted heteroaryl, C_7-9phenylalkyl, and substituted C_7-9phenylalkyl; and

In certain embodiments of compounds of Formula (I), each of the one or more substituent groups is independently chosen from halogen, C_1-3alkyl, —OH, —NH₂, —SH, —COOH, C_1-3alkoxy, C_1-3acyl, C_1-3thioalkyl, C_1-3alkoxycarbonyl, C_1-3alkylamino, and C_1-3dialkylamino.

Within the scope of this disclosure, it is to be understood that when R⁵is an oxo group the bond between R⁵and the carbon to which it is bonded is a double bond.

In certain embodiments, each of R⁶, R⁷and R⁸is hydrogen.

In certain embodiments, R⁴is chosen from ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, and diethoxymethyl.

In certain embodiments, R⁴is ethyl.

In certain embodiments, R⁴is n-propyl.

In certain embodiments, R⁴is n-butyl.

In certain embodiments, R⁴is diethoxymethyl.

In certain embodiments, R⁴is cyclohexylmethyl.

In certain embodiments, R⁴is benzyl.

In certain embodiments, R⁵is hydrogen, hydroxy, fluoro, oxo, or 4-chlorophenyl. In other embodiments, R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, R⁵is hydrogen, hydroxy, fluoro, oxo, or 4-chlorophenyl, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In other embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of compounds of Formula (I), R¹is chosen from C_1-6alkyl, substituted C_1-6alkyl, C_3-6cycloalkyl, phenyl, substituted phenyl, C_7-9phenylalkyl, and pyridyl. In other embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl, cyclohexyl, or 3-pyridyl.

In certain embodiments of compounds of Formula (I), R¹is chosen from propyl, isopropyl, tert-butyl, cyclohexyl, and phenyl.

In certain embodiments of compounds of Formula (I), R²is chosen from hydrogen, methyl, and isopropyl; and R³is hydrogen.

In certain embodiments of compounds of Formula (I), R³is hydrogen.

In certain embodiments of compounds of Formula (I), R⁴is n-butyl.

In certain embodiments of compounds of Formula (I), R⁵is chosen from hydrogen and hydroxy.

In certain embodiments of compounds of Formula (I), R¹is chosen from propyl, isopropyl, tert-butyl, cyclohexyl, and phenyl; R²is chosen from hydrogen, methyl, and isopropyl; R⁴is n-butyl; and each of R³, R⁵, R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of compounds of Formula (I), R²and R³is chosen from hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, cycloalkyl, substituted cycloalkyl, cycloalkoxycarbonyl, substituted cycloalkoxycarbonyl, heteroaryl, substituted heteroaryl, heteroarylalkyl and substituted heteroarylalkyl. In certain embodiments of compounds of Formula (I), R²and R³is chosen from hydrogen, C_1-4alkyl, substituted C_1-4alkyl, C_1-4alkoxycarbonyl, C_3-6cycloalkyl, C_3-6cycloalkoxycarbonyl, phenyl, substituted phenyl, C_7-9phenylalkyl, and pyridyl. In certain embodiments of compounds of Formula (I), R²and R³is chosen from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, cyclohexyloxycarbonyl, phenyl, benzyl, phenethyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. In certain embodiments of compounds of Formula (I), R²is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, cyclohexyloxycarbonyl, phenyl, benzyl, phenethyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and R³is hydrogen. In certain embodiments of compounds of Formula (I), R²is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, phenyl, or cyclohexyl, and R³is hydrogen. In certain embodiments of a compound of Formula (I), R²is methyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, or cyclohexyloxycarbonyl, and R³is methyl.

In certain embodiments of a compound of Formula (I), R²and R³together with the carbon atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, or substituted cycloheteroalkyl ring. In certain embodiments of compounds of Formula (I), R²and R³together with the carbon atom to which they are bonded form a cyclobutyl, cyclopentyl, or cyclohexyl ring.

In certain embodiments of a compound of Formula (I), R¹is chosen from C_1-6alkyl, substituted C_1-6alkyl, C_3-6cycloalkyl, phenyl, substituted phenyl, C_7-9phenylalkyl, and pyridyl, R²and R³is chosen from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, cyclohexyloxycarbonyl, phenyl, benzyl, phenethyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. In certain of the above embodiments, R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and in certain embodiments, R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl, cyclohexyl, or 3-pyridyl. In certain of the above embodiments of a compound of Formula (I), R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, in certain embodiments, R⁴is ethyl, n-propyl, n-butyl, diethoxymethyl, cyclohexylmethyl, or benzyl, R⁵is hydrogen, hydroxy, fluoro, oxo, or 4-chlorophenyl, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is chosen from C_1-6alkyl, substituted C_1-6alkyl, C_3-6cycloalkyl, phenyl, substituted phenyl, C_7-9phenylalkyl and pyridyl, R²is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, phenyl, or cyclohexyl, and R³is hydrogen. In certain of the above embodiments, R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and in certain embodiments, R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl, cyclohexyl, or 3-pyridyl. In certain of the above embodiments of a compound of Formula (I), R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, and in certain embodiments, R⁴is ethyl, n-propyl, n-butyl, diethoxymethyl, cyclohexylmethyl, or benzyl, R⁵is hydrogen, hydroxy, fluoro, oxo, or 4-chlorophenyl, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I) R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl, cyclohexyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, R²is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, phenyl, or cyclohexyl, R³is hydrogen, R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl, cyclohexyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is ethyl, n-propyl, n-butyl, cyclohexylmethyl, benzyl, or diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷and R⁸is hydrogen. In certain embodiments of compounds of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, methyl, n-propyl, or isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopropylmethyl, R¹is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclobutylmethyl, R¹is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵¹is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R¹is methyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl; isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R³is ethyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In other embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is allyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is propargyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R²is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I) R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶; R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is ethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is tert-butyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is neopentyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-hexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-heptyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is allyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is propargyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is benzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydroxy, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxy benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁵is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is independently hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is independently hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is independently hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I) R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I), R¹methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is tert-butyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is neopentyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-hexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-heptyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is allyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is propargyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, and each of R⁶, R⁷, and R⁸is hydrogen. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S configuration.

In certain embodiments of a compound of Formula (I) R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1 hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is methyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is ethyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁵is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I) R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is propargyl, R¹is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl; isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is phenyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is tert-butyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is isopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is sec-pentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is neopentyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-hexyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-heptyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is allyl, R⁵is oxo, and each of R⁶, R⁷; and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methylallyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-enyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is propargyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-2-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is but-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is pent-3-ynyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexyl, R⁵is oxo, and each of R⁶, R⁷and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopropylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclobutylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclopentylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cycloheptylmethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 2-methoxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-methoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 3-ethoxypropyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxyisobutyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is 1-hydroxybenzyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, and each of R⁶, R⁷, and R⁸is hydrogen.

In certain embodiments of a compound of Formula (I), R¹is chosen from C_1-6alkyl, substituted C_1-6alkyl, C_3-6cycloalkyl, phenyl, substituted phenyl, C_7-9phenylalkyl and pyridyl, R²is chosen from hydrogen, C_1-4alkyl, substituted C_1-4alkyl, C_1-4alkoxycarbonyl, C_3-6cycloalkyl, C_3-6cycloalkoxycarbonyl, phenyl, substituted phenyl, C_7-9phenylalkyl and pyridyl, R³is hydrogen, R⁴is chosen from C_2-6alkyl, substituted C_2-6alkyl, benzyl, substituted benzyl, C_4-7cycloalkyl, C_3-7cycloalkylmethyl and dialkoxymethyl, R⁵is chosen from hydrogen, hydroxy, mercapto, fluoro, oxo, C_1-4alkyl, aryl, substituted aryl, C_3-6cycloalkyl, heteroaryl, substituted heteroaryl, C_7-9phenylalkyl and substituted C_7-9phenylalkyl, each of R⁶and R⁷is hydrogen, and R⁸is C_7-9phenylalkyl, or substituted C_7-9phenylalkyl. In certain of the above embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and in certain embodiments, R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl, cyclohexyl, or 3-pyridyl. In certain of the above embodiments of a compound of Formula (I), R²is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and in certain embodiments, R²is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclohexyl, or phenyl. In certain of the above embodiments of a compound of Formula (I), R⁴is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, n-heptyl, allyl, 2-methylallyl, but-3-enyl, propargyl, but-2-ynyl, but-3-ynyl, pent-3-ynyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 1-hydroxyethyl, 1-hydroxybutyl, 1-hydroxyisobutyl, benzyl, 1-hydroxybenzyl, or diethoxymethyl, and in certain embodiments, R⁴is ethyl, n-propyl, n-butyl, diethoxymethyl, cyclohexylmethyl, or benzyl. In certain of the above embodiments of a compound of Formula (I), R⁵is hydrogen, hydroxy, fluoro, oxo, or 4-chlorophenyl. In certain of the above embodiments of a compound of Formula (I), R⁸is 3,5-dichlorobenzyl, 1-(3-chlorophenyl)ethyl, 1-(3,4-dichlorophenyl)ethyl, 1-(3-chloro-4-iodophenyl)ethyl, 1-(4-chloro-3-iodophenyl)ethyl, 3,4-dimethylbenzyl, 1-(2,4-dimethoxyphenyl)ethyl, 1-(2,5-dimethoxyphenyl)ethyl, 1-(2,6-dimethoxyphenyl)ethyl, 1-(3,4-dimethoxyphenyl)ethyl, 1-(3,5-dimethoxyphenyl)ethyl, 1-(3,4,5-trimethoxyphenyl)ethyl, 3-carboxybenzyl, 3-cyanobenzyl, 4-carboxybenzyl, 4-cyanobenzyl, 1-(3-carboxyphenyl)ethyl, 1-(3-cyanophenyl)ethyl, 1-(4-carboxyphenyl)ethyl, 1-(4-cyanophenyl)ethyl, 3-phenylprop-2-yl, 2-(3,4-dichlorophenyl)propyl, 3-(3,4-dichlorophenyl)prop-2-yl, or 3-phenyl-3-hydroxyprop-2-yl, and in certain embodiments R⁸is 1-(3,4-dichlorophenyl)ethyl, 1-(3-carboxyphenyl)ethyl, 1-(4-carboxyphenyl)ethyl, 3,5-dichlorobenzyl, 3-carboxybenzyl, or 4-carboxybenzyl.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-propyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isopropyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is n-butyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is isobutyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is sec-butyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is ethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-propyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is n-butyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is tert-butyl, R³is hydrogen, R⁴is benzyl, R⁵is fluoro, each of R⁶and R⁷is hydrogen, and R⁸is 1-(3,4-dichlorophenyl)ethyl. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the S-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the S-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration. In certain of the above embodiments of a compound of Formula (I), the carbon to which R⁵is bonded is of the R-configuration and the α-carbon of the 1-(3,4-dichlorophenyl)ethyl group is of the R-configuration.

In certain embodiments of a compound of Formula (I): R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is ethyl, R⁵is oxo, each of R⁶and R⁷is hydrogen, and R⁸is 3,5-dichlorobenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-propyl, R⁵is oxo, each of R⁶and R⁷is hydrogen, and R⁸is 3,5-dichlorobenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is n-butyl, R⁵is oxo, each of R⁶and R⁷is hydrogen, and R⁸is 3,5-dichlorobenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is diethoxymethyl, R⁵is oxo, each of R⁶and R⁷is hydrogen, and R⁸is 3,5-dichlorobenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is oxo, each of R⁶and R⁷is hydrogen, and R⁸is 3,5-dichlorobenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is cyclohexyl, R³is hydrogen, R⁴is benzyl, R⁵is oxo, each of R⁶and R⁷is hydrogen, and R⁸is 3,5-dichlorobenzyl.

In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl; n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is ethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 3-carboxybenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-propyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 3-carboxybenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is n-butyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 3-carboxybenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is diethoxymethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 3-carboxybenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is cyclohexylmethyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 3-carboxybenzyl. In certain embodiments of a compound of Formula (I), R¹is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, phenyl, cyclohexyl, or 3-pyridyl, R²is hydrogen, R³is hydrogen, R⁴is benzyl, R⁵is hydrogen, each of R⁶and R⁷is hydrogen, and R⁸is 3-carboxybenzyl.

In certain embodiments of a compound of Formula (I), the compound is chosen from:

3-{[1-isobutanoyloxyethoxy]carbonylamino}propyl(n-butyl)phosphinic acid;
3-{[benzoyloxyethoxy]carbonylamino}propyl(n-butyl)phosphinic acid;
3-{[1-isobutanoyloxymethoxy]carbonylamino}propyl(n-butyl)phosphinic acid;
3-{[benzoyloxymethoxycarbonylamino}propyl(n-butyl)phosphinic acid;
3-{[1-isobutanoyloxyisobutoxy]carbonylamino}propyl(n-butyl)phosphinic acid;
(3-{[1-cyclohexanoyloxyethoxy]carbonylamino}propyl(n-butyl)phosphinic acid;
3-{[1-isobutanoyloxyisobutoxy]carbonylamino}propyl(n-butyl)phosphinic acid sodium salt;
3-{[butanoyloxyethoxy]carbonylamino}propyl(n-butyl)phosphinic acid sodium salt;

a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable solvate of any of the foregoing.

Synthesis

The compounds disclosed herein may be obtained via the synthetic method illustrated in Scheme 1. Those of ordinary skill in the art will appreciate that a synthetic route to the disclosed compounds consists of attaching promoieties to 3-aminopropylphosphinic acid analogs. Numerous methods have been described in the art for the synthesis of 3-aminopropylphosphinic acid analog GABA_Bantagonists (e.g. Froestl et al., J. Med. Chem. 1995, 38, 3313-3331; Dingwall et al., Tetrahedron 1989, 45, 3787-3808; Deprele and Montchamp, J. Org. Chem. 2001, 66, 6745-6755; Dingwall et al., U.S. Pat. No. 4,656,298; Baylis et al., U.S. Pat. No. 5,013,863; Baylis et al., U.S. Pat. No. 5,051,524; Baylis et al., U.S. Pat. No. 5,300,679; Marescaux et al., U.S. Pat. No. 5,229,379; Marescaux et al., U.S. Pat. No. 5,407,922; Mickel et al., U.S. Pat. No. 5,332,729; Mickel, U.S. Pat. No. 5,376,684; and Mickel et al., U.S. Pat. No. 5,424,441). General synthetic methods useful in the synthesis of the compounds described herein are available in the art (see, e.g., Wuts and Greene, “Protective Groups in Organic Synthesis,” John Wiley & Sons, 4th ed. 2007; Harrison et al., “Compendium of Organic Synthetic Methods,” Vols. 1-11, John Wiley & Sons 1971-2003; Larock “Comprehensive Organic Transformations,” John Wiley & Sons, 2nd ed. 2000; and Paquette, “Encyclopedia of Reagents for Organic Synthesis,” John Wiley & Sons, 11th ed. 2003). Accordingly, starting materials useful for preparing compounds and intermediates thereof, and/or practicing methods described herein are commercially available or may be prepared by well-known synthetic methods. Other methods for synthesis of the prodrugs described herein are either described in the art or will be readily apparent to the skilled artisan in view of the references provided above and may be used to synthesize the compounds described herein. Accordingly, the methods presented in the Schemes herein are illustrative rather than comprehensive.

A method for synthesis of compounds of Formula (I), illustrated in Scheme 1, relies upon reaction of a 3-aminopropylphosphinic acid analog of Formula (II) with a 1-(acyloxy)-alkyl N-hydroxysuccinimidyl carbonate compound of Formula (III), optionally in the presence of a base, as described in the co-pending application Gallop et al., International Publication No. WO 2005/066122 entitled “Synthesis of Acyloxyalkyl Carbamate Prodrugs and Intermediates Thereof,” filed Dec. 30, 2004.

wherein:

R⁹and R¹⁰is chosen from hydrogen, acylamino, acyloxy, alkoxycarbonylamino, alkoxycarbonyloxy, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, arylalkyl, carbamoyloxy, dialkylamino, heteroaryl, hydroxy, and sulfonamido, or R⁹and R¹⁰together with the atoms to which they are bonded form a substituted cycloalkyl, substituted cycloheteroalkyl, or substituted aryl ring; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷and R⁸are as previously defined.

In certain embodiments of the method described in Scheme 1 for synthesizing a compound of Formula (I), R²and R³in the compound of Formula (III) are different, such that the carbon atom to which these substituents are bonded is a stereogenic center. In certain embodiments of the method for synthesizing a compound of Formula (I), R²and R³in the compound of Formula (I) are different and the compound of Formula (I) is substantially one diastereomer.

In certain embodiments of the method described in Scheme 1 for synthesizing a compound of Formula (I), R⁹and R¹⁰in the compound of Formula (III) are each benzoyloxy, the stereochemistry at the carbon to which R⁹is bonded is of the R-configuration, and the stereochemistry at the carbon to which R¹⁰is bonded is of the R-configuration. In certain embodiments of the method described in Scheme 1 for synthesizing a compound of Formula (I), R⁹and R¹⁰in the compound of Formula (III) are each benzoyloxy, the stereochemistry at the carbon to which R⁹is bonded is of the S-configuration and the stereochemistry at the carbon to which R¹⁰is bonded is of the S-configuration.

In certain embodiments, the method of Scheme 1 is carried out in a solvent. Useful solvents include, but are not limited to, acetone, acetonitrile, dichloromethane, dichloroethane, chloroform, toluene, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, dimethyl sulfoxide, pyridine, ethyl acetate, methyl tert-butyl ether, methanol, ethanol, isopropanol, tert-butanol, water, or combinations thereof. In certain embodiments, the solvent is acetone, acetonitrile, dichloromethane, toluene, tetrahydrofuran, pyridine, methyl tert-butyl ether, methanol, ethanol, isopropanol, water, or combinations thereof. In certain embodiments, the solvent is a mixture of acetonitrile and water. In certain embodiments, the solvent is a mixture of acetonitrile and water, with a volume ratio of acetonitrile to water from about 1:5 to about 5:1. In certain embodiments, the solvent is a mixture of tetrahydrofuran and water, with a volume ratio of tetrahydrofuran to water from about 20:1 to about 2:1. In certain embodiments, the solvent is a mixture of methyl tert-butyl ether and water. In certain embodiments, the solvent is a mixture of methyl tert-butyl ether and water, with a volume ratio of methyl tert-butyl ether to water from about 20:1 to about 2:1. In certain embodiments, the solvent is a mixture of methyl tert-butyl ether and water, wherein the methyl tert-butyl ether contains from about 10% to about 50% acetone by volume. In certain embodiments, the solvent is dichloromethane, water, or a combination thereof. In certain embodiments, the solvent is a biphasic mixture of dichloromethane and water. In certain embodiments, the solvent is a biphasic mixture of dichloromethane and water containing from about 0.001 equivalents to about 0.1 equivalents of a phase transfer catalyst. In certain embodiments, the phase transfer catalyst is a tetraalkylammonium salt, and in certain embodiments, the phase transfer catalyst is a tetrabutylammonium salt.

The method of Scheme 1 may be carried out at a temperature from about −20° C. to about 40° C. In certain embodiments, the temperature is from about −20° C. to about 25° C. In certain embodiments, the temperature is from about 0° C. to about 25° C. In certain embodiments, the temperature is from about 25° C. to about 40° C.

In certain embodiments of the method of Scheme 1, the reaction is performed in the absence of a base.

In other embodiments of the method of Scheme 1, the reaction is performed in the presence of an inorganic base. In certain embodiments, the reaction is performed in the presence of an alkali metal bicarbonate or alkali metal carbonate salt. In other embodiments, the reaction is performed in the presence of sodium bicarbonate.

In certain embodiments of the method of Scheme 1, the reaction is performed in the presence of an organic base. In certain embodiments, the reaction is performed in the presence of triethylamine, tributylamine, diisopropylethylamine, dimethylisopropylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, pyridine, 2-methylpyridine, 2,6-dimethylpyridine, 4-dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane, 1, 8-diazabicyclo[5.4.0]undec-7-ene, or 1,5-diazabicyclo[4.3.0]undec-7-ene, and in certain embodiments, the reaction is performed in the presence of triethylamine, diisopropylethylamine, N-methylmorpholine, or pyridine.

Pharmaceutical Compositions

Pharmaceutical compositions comprising a therapeutically effective amount of one or more 3-aminopropylphosphinic acid analog prodrug compounds of Formula (I), in certain embodiments, in purified form, together with a suitable amount of a pharmaceutically acceptable vehicle, so as to provide a form for proper administration to a patient are provided herein. Suitable pharmaceutical vehicles include excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol, and the like. The present compositions, if desired, may also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. In addition, auxiliary, stabilizing, thickening, lubricating, and coloring agents may be used.

Pharmaceutical compositions may be manufactured by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes. Pharmaceutical compositions may be formulated in conventional manner using one or more physiologically acceptable carriers, diluents, excipients, or auxiliaries, which facilitate processing of compounds disclosed herein into preparations, which may be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.

Pharmaceutical compositions may take the form of solutions, suspensions, emulsion, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. In certain embodiments, the pharmaceutically acceptable vehicle is a capsule (see e.g., Grosswald et al., U.S. Pat. No. 5,698,155). Other examples of suitable pharmaceutical vehicles have been described in the art (see Remington's Pharmaceutical Sciences, Philadelphia College of Pharmacy and Science, 19th Edition, 1995). In certain embodiments, compositions are formulated for oral delivery, particularly for oral sustained release administration.

Pharmaceutical compositions for oral delivery may be in the form of tablets, lozenges, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups, or elixirs, for example. Orally administered compositions may comprise one or more optional agents, for example, sweetening agents such as fructose, aspartame, and saccharin; flavoring agents such as peppermint, oil of wintergreen, and cherry; coloring agents; and preserving agents, to provide a pharmaceutically palatable preparation. Moreover, when in tablet or pill form, the compositions may be coated to delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained action over an extended period of time. Oral compositions may include standard vehicles such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Such vehicles may be of pharmaceutical grade.

For oral liquid preparations such as, for example, suspensions, elixirs and solutions, suitable carriers, excipients or diluents include water, saline, alkyleneglycols (e.g., propylene glycol), polyalkylene glycols (e.g., polyethylene glycol), oils, alcohols, slightly acidic buffers having a pH ranging from about pH 4 to about pH 6 (e.g., acetate, citrate, ascorbate at between about 5 mM to about 50 mM), etc. Additionally, flavoring agents, preservatives, coloring agents, bile salts, acylcarnitines, and the like may be added.

When the compounds of Formula (I) are acidic, they may be included in any of the above-described formulations as free acids, pharmaceutically acceptable salts, solvates, or hydrates. Pharmaceutically acceptable salts substantially retaining the activity of the free acid forms may be prepared by reaction with bases, and tend to be more soluble in aqueous and other protic solvents than the corresponding free acid forms. In certain embodiments, sodium salts of a compound of Formula (I) are used in the above described formulations.

Sustained Release Oral Dosage Forms

The disclosed compounds may be used with a number of different dosage forms, which may be adapted to provide sustained release of a compound of Formula (I) upon oral administration.

In certain embodiments, dosage forms comprise beads, which on dissolution or diffusion release a compound of Formula (I) over an extended period of hours, in certain embodiments over a period of at least about 6 hours, and in certain embodiments, over a period of at least about 8 hours and in certain embodiments, over a period of at least about 12 hours. The beads may have a central composition or core comprising a compound disclosed herein and pharmaceutically acceptable vehicles, including an optional lubricant, antioxidant, and buffer. The beads may be medical preparations with a diameter of about 0.05 mm to about 2 mm. Individual beads may comprise doses of a compound of Formula (I), for example, doses of up to about 40 mg of compound. The beads, in certain embodiments, are formed of non-cross-linked materials to enhance their discharge from the gastrointestinal tract. The beads may be coated with a release rate-controlling polymer that gives a timed-release profile.

The time-release beads may be manufactured into a tablet for therapeutically effective administration. The beads may be made into matrix tablets by the direct compression of a plurality of beads coated with, for example, an acrylic resin and blended with excipients such as hydroxypropylmethyl cellulose. The manufacture of beads is disclosed in the art (Lu, Int. J. Pharm. 1994, 112, 117-124; Pharmaceutical Sciences by Remington, 14^thed, pp. 1626-1628 (1970); Fincher, J. Pharm. Sci. 1968, 57, 1825-1835; and U.S. Pat. No. 4,083,949), as has the manufacture of tablets (Pharmaceutical Sciences, by Remington, 17^thEd, Ch. 90, pp. 1603-1625 (1985)).

One type of sustained release oral dosage formulation that may be used with the compounds of Formula (I) comprises an inert core, such as a sugar sphere, coated with an inner drug-containing layer and an outer membrane layer controlling drug release from the inner layer. A sealcoat may be provided between the inert core and the layer containing the active ingredient. When the core is of a water-soluble or water-swellable inert material, the sealcoat may be in the form of a relatively thick layer of a water-insoluble polymer. Such a controlled release beads may thus comprise: (i) a core unit of a substantially water-soluble or water-swellable inert material; (ii) a first layer on the core unit of a substantially water-insoluble polymer; (iii) a second layer covering the first layer and containing an active ingredient; and (iv) a third layer on the second layer of polymer effective for controlled release of the active ingredient, wherein the first layer is adapted to control water penetration into the core.

In certain embodiments, the first layer (ii) above constitutes more than about 2% (w/w) of the final bead composition, such as more than about 3% (w/w), e.g., from about 3% to about 80% (w/w). The amount of the second layer (ii) above usually constitutes from about 0.05% to about 60% (w/w), such as from about 0.1% to about 30% (w/w) of the final bead composition. The amount of the third layer (iv) above usually constitutes from about 1% to about 50% (w/w), for example, from about 2% to about 25% (w/w) of the final bead composition. The core unit may have a size from about 0.05 to about 2 mm. The controlled release beads may be provided in a multiple unit formulation, such as a capsule or a tablet.

The cores may be of a water-soluble or swellable material and may be any such material that is conventionally used as cores or any other pharmaceutically acceptable water-soluble or water-swellable material made into beads or pellets. The cores may be spheres of materials such as sucrose/starch (Sugar Spheres NF), sucrose crystals, or extruded and dried spheres typically comprising excipients such as microcrystalline cellulose and lactose. The substantially water-insoluble material in the first, or sealcoat layer is generally a “GI insoluble” or “GI partially insoluble” film forming polymer (dispersed or dissolved in a solvent). Examples include, but are not limited to, ethyl cellulose, cellulose acetate, and cellulose acetate butyrate, polymethacrylates such as ethyl acrylate/methyl methacrylate copolymer (Eudragit NE-30-D), ammonio methacrylate copolymer types A and B (Eudragit RL30D and RS30D), and silicone elastomers. A plasticizer is used together with the polymer. Exemplary plasticizers include, but are not limited to, dibutylsebacate, propylene glycol, triethylcitrate, tributylcitrate, castor oil, acetylated monoglycerides, acetyl triethylcitrate, acetyl butylcitrate, diethyl phthalate, dibutyl phthalate, triacetin, and fractionated coconut oil (medium-chain triglycerides). The second layer containing the active ingredient may comprise the active ingredient with or without a polymer as a binder. The binder, when used, may be hydrophilic but may be water-soluble or water-insoluble. Examples of polymers that may be used in the second layer containing the active drug are hydrophilic polymers such as, for example, polyvinylpyrrolidone (PVP), polyalkylene glycol such as polyethylene glycol, gelatine, polyvinyl alcohol, starch, and derivatives thereof, cellulose derivatives, such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxyethyl cellulose, and carboxymethylhydroxyethyl cellulose, acrylic acid polymers, polymethacrylates, and any other appropriate pharmaceutically acceptable polymer. The ratio of drug to hydrophilic polymer in the second layer is usually in the range of from about 1:100 to about 100:1 (w/w). Suitable polymers for use in the third layer, or membrane, for controlling the drug release may be chosen from water-insoluble polymers or polymers with pH-dependent solubility, such as, for example, ethyl cellulose, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, polymethacrylates, or combinations thereof, optionally combined with plasticizers, such as those mentioned above. Optionally, a controlled release layer comprises, in addition to the polymers above, other substance(s) with different solubility characteristics, to adjust the permeability and thereby the release rate, of the controlled release layer. Examples of polymers that may be used as a modifier together with, for example, ethyl cellulose include, but are not limited to, HPMC, hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose, carboxymethylcellulose, polyethylene glycol, polyvinylpyrrolidone (PVP), polyvinyl alcohol, polymers with pH-dependent solubility, such as cellulose acetate phthalate or ammonio methacrylate copolymer and methacrylic acid copolymer, and combinations thereof. Additives such as sucrose, lactose and pharmaceutical grade surfactants may also be included in the controlled release layer, if desired.

The preparation of the multiple unit formulation may comprise the additional step of transforming the prepared beads into a pharmaceutical formulation, such as by filling a predetermined amount of the beads into a capsule, or compressing the beads into tablets. Examples of multi-particulate sustained release oral dosage forms are described in, for example, U.S. Pat. Nos. 6,627,223 and 5,229,135.

In certain embodiments, an oral sustained release pump may be used (see Langer, supra; Sefton, CRC Crit Ref Biomed. Eng. 1987, 14, 201; Saudek et al., N. Engl. J Med. 1989, 321, 574).

In certain embodiments, polymeric materials may be used (see “Medical Applications of Controlled Release,” Langer and Wise (eds.), CRC Press., Boca Raton, Fla. (1974); “Controlled Drug Bioavailability,” Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Langer et al., J Macromol. Sci. Rev. Macromol Chem. 1983, 23, 61; see also Levy et al., Science 1985, 228, 190; During et al., Ann. Neurol. 1989, 25, 351; Howard et al., J. Neurosurg. 1989, 71, 105). In certain embodiments, polymeric materials may be used for oral sustained release delivery. Polymers include, but are not limited to, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydroxyethylcellulose (especially, hydroxypropylmethylcellulose). Other cellulose ethers are described (Alderman, Int. J. Pharm. Tech. & Prod. Mfr. 1984, 5(3), 1-9). Factors affecting drug release are well known to the skilled artisan and are described in the art (Bamba et al., Int. J. Pharm. 1979, 2, 307).

In certain embodiments, enteric-coated preparations may be used for oral sustained release administration. Examples of coating materials include polymers with a pH-dependent solubility (i.e., pH-controlled release), polymers with a slow or pH-dependent rate of swelling, dissolution or erosion (i.e., time-controlled release), polymers that are degraded by enzymes (i.e., enzyme-controlled release), and polymers that form firm layers that are destroyed by an increase in pressure (i.e., pressure-controlled release).

In certain embodiments, drug-releasing lipid matrices may be used for oral sustained release administration. An example is solid microparticles of a compound of Formula (I) coated with a thin controlled release layer of a lipid (e.g., glyceryl behenate and/or glyceryl palmitostearate) as disclosed in Farah et al., U.S. Pat. No. 6,375,987 and Joachim et al., U.S. Pat. No. 6,379,700. The lipid-coated particles may optionally be compressed to form a tablet. Another controlled release lipid-based matrix material that is suitable for sustained release oral administration comprises polyglycolized glycerides as disclosed in Roussin et al., U.S. Pat. No. 6,171,615.

In certain embodiments, waxes may be used for oral sustained release administration. Examples of suitable sustained compound-releasing waxes are disclosed in Cain et al., U.S. Pat. No. 3,402,240 (carnauba wax, candelilla wax, esparto wax, and ouricury wax); Shtohryn et al., U.S. Pat. No. 4,820,523 (hydrogenated vegetable oil, bees wax, carnauba wax, paraffin, candelilla, ozokerite, and combinations thereof); and Walters, U.S. Pat. No. 4,421,736 (combination of paraffin and castor wax).

In certain embodiments, osmotic delivery systems may be used for oral sustained release administration (Verma et al., Drug Dev. Ind. Pharm. 2000, 26, 695-708). In certain embodiments, OROS® systems made by Alza Corporation, Mountain View, Calif. may be used for oral sustained release delivery devices (Theeuwes et al., U.S. Pat. No. 3,845,770; Theeuwes et al., U.S. Pat. No. 3,916,899).

In certain embodiments, a controlled-release system may be placed in proximity of the target of a compound disclosed herein (e.g., within the spinal cord), thus requiring only a fraction of the systemic dose (see e.g., Goodson, in “Medical Applications of Controlled Release,” supra, vol. 2, pp. 115-138 (1984)). Other controlled-release systems discussed in Langer, Science 1990, 249, 1527-1533, may also be used.

In certain embodiments, dosage forms comprise a compound of Formula (I) coated on a polymer substrate. The polymer may be an erodible, or a nonerodible polymer. The coated substrate may be folded onto itself to provide a bilayer polymer drug dosage form. For example, a compound disclosed of Formula (I) gelatin, polyvinyl alcohol, polyorthoester, polyacetyl, or a polyorthocarbonate and the coated polymer folded onto itself to provide a bilaminated dosage form. In operation, the bioerodible dosage form erodes at a controlled rate to dispense a compound of Formula (I) over a sustained release period. Examples of useful biodegradable polymers include biodegradable poly(amides), poly(amino acids), poly(esters), poly(lactic acid), poly(glycolic acid), poly(carbohydrate), poly(orthoester), poly (orthocarbonate), poly(acetyl), poly(anhydrides), biodegradable poly(dihydropyrans), and poly(dioxinones), which are known in the art (Rosoff, Controlled Release of Drugs Chap. 2, pp. 53-95 (1989); and in U.S. Pat. Nos. 3,811,444, 3,962,414, 4,066,747, 4,070,347, 4,079,038, and 4,093,709).

In certain embodiments, dosage forms comprise a compound of Formula (I) loaded into a polymer that releases the compound by diffusion through a polymer, or by flux through pores or by rupture of a polymer matrix. Drug delivery polymeric dosage forms comprise between about 2 mg to about 500 mg of compound homogenously contained in or on a polymer. The dosage forms comprise at least one exposed surface at the beginning of dose delivery. The non-exposed surface, when present, is coated with a pharmaceutically acceptable material impermeable to the passage of a compound. The dosage forms may be manufactured by procedures known in the art. An example of providing the dosage forms comprise blending a pharmaceutically acceptable carrier like polyethylene glycol, with a known dose of a compound at an elevated temperature, (e.g., about 37° C.), and adding it to a silastic medical grade elastomer with a cross-linking agent, for example, octanoate, followed by casting in a mold. The step is repeated for each optional successive layer. The system is allowed to set for about 1 hour, to provide the dosage form. Representative polymers for manufacturing the dosage form are chosen from olefinic polymers, vinyl polymers, addition polymers, condensation polymers, carbohydrate polymer and silicone polymers such as polyethylene, polypropylene, polyvinyl acetate, polymethylacrylate, polyisobutylmethacrylate, poly alginate, polyamide, and polysilicone. The polymers and procedures for manufacturing the polymers are described in the art (Coleman et al., Polymers 1990, 31, 1187-1231; Roerdink et al., Drug Carrier Systems 1989, 9, 57-10; Leong et al., Adv. Drug Delivery Rev. 1987, 1, 199-233; Roff et al., Handbook of Common Polymers 1971, CRC Press; and U.S. Pat. No. 3,992,518).

In certain embodiments, dosage forms comprise a plurality of pills. The time-release pills provide a number of individual doses for providing various time doses for achieving a sustained-release prodrug delivery profile over an extended period of time up to about 24 hours. The matrix comprises a hydrophilic polymer chosen from, for example, a polysaccharide, agar, agarose, natural gum, alkali alginate including sodium alginate, carrageenan, fucoidan, furcellaran, laminaran, hypnea, gum arabic, gum ghatti, gum karaya, gum tragacanth, locust bean gum, pectin, amylopectin, gelatin, and a hydrophilic colloid. The hydrophilic matrix comprises a plurality of about 4 to about 50 pills, each pill comprises a dose population of from about 10 ng, about 0.5 mg, about 1 mg, about 1.2 mg, about 1.4 mg, about 1.6 mg, about 5.0 mg, etc. The pills comprise a release rate-controlling wall of about 0.001 mm up to about 10 mm thickness to provide for the timed release of a compound. Examples of wall forming materials include a triglyceryl ester chosen from glyceryl tristearate, glyceryl monostearate, glyceryl dipalmitate, glyceryl laureate, glyceryl didecenoate, and glyceryl tridenoate. Other wall forming materials include polyvinyl acetate, phthalate, methylcellulose phthalate, and microporous olefins. Procedures for manufacturing pills are disclosed in U.S. Pat. Nos. 4,434,153, 4,721,613, 4,853,229, 2,996,431, 3,139,383, and 4,752,470.

In certain embodiments, dosage forms comprise an osmotic dosage form, which comprises a semipermeable wall that surrounds a therapeutic composition comprising the compound. In use within a patient, the osmotic dosage form comprising a homogenous composition, imbibes fluid through the semipermeable wall into the dosage form in response to the concentration gradient across the semipermeable wall. The therapeutic composition in the dosage form develops osmotic pressure differential that causes the therapeutic composition to be administered through an exit from the dosage form over a prolonged period of time up to about 24 hours (or even in some cases up to about 30 hours) to provide controlled and sustained compound release. These delivery platforms may provide an essentially zero order delivery profile as opposed to the spiked profiles of immediate release formulations.

In certain embodiments, a dosage form comprises another osmotic dosage form comprising a wall surrounding a compartment, the wall comprising a semipermeable polymeric composition permeable to the passage of fluid and substantially impermeable to the passage of compound present in the compartment, a compound-containing layer composition in the compartment, a hydrogel push layer composition in the compartment comprising an osmotic formulation for imbibing and absorbing fluid for expanding in size for pushing the compound composition layer from the dosage form, and at least one passageway in the wall for releasing the prodrug composition. The method delivers the compound by imbibing fluid through the semipermeable wall at a fluid imbibing rate determined by the permeability of the semipermeable wall and the osmotic pressure across the semipermeable wall causing the push layer to expand, thereby delivering the compound from the dosage form through the exit passageway to a patient over a prolonged period of time (up to about 24 or even about 30 hours). The hydrogel layer composition may comprise about 10 mg to about 1000 mg of a hydrogel such as a member chosen from a polyalkylene oxide of about 1,000,000 to about 8,000,000 weight-average molecular weight, which are chosen from a polyethylene oxide of about 1,000,000 weight-average molecular weight, a polyethylene oxide of about 2,000,000 molecular weight, a polyethylene oxide of about 4,000,000 molecular weight, a polyethylene oxide of about 5,000,000 molecular weight, a polyethylene oxide of about 7,000,000 molecular weight, and a polypropylene oxide of the about 1,000,000 to about 8,000,000 weight-average molecular weight; or about 10 mg to about 1000 mg of an alkali carboxymethylcellulose of about 10,000 to about 6,000,000 weight average molecular weight, such as sodium carboxymethylcellulose or potassium carboxymethylcellulose. The hydrogel expansion layer comprises about 0.0 mg to about 350 mg, in present manufacture; about 0.1 mg to about 250 mg of a hydroxyalkylcellulose of about 7,500 to about 4,500,00 weight-average molecular weight (e.g., hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, or hydroxypentylcellulose) in present manufacture; about 1 mg to about 50 mg of an agent chosen from sodium chloride, potassium chloride, potassium acid phosphate, tartaric acid, citric acid, raffinose, magnesium sulfate, magnesium chloride, urea, inositol, sucrose, glucose, and sorbitol; about 0 to about 5 mg of a colorant, such as ferric oxide; about 0 mg to about 30 mg, in a present manufacture, about 0.1 mg to about 30 mg of a hydroxypropylalkylcellulose of about 9,000 to about 225,000 average-number molecular weight, chosen from hydroxypropylethylcellulose, hydroxypropypentylcellulose, hydroxypropylmethylcellulose, and hydropropylbutylcellulose; about 0.00 to about 1.5 mg of an antioxidant chosen from ascorbic acid, butylated hydroxyanisole, butylated hydroxyquinone, butylhydroxyanisol, hydroxycoumarin, butylated hydroxytoluene, cephalm, ethyl gallate, propyl gallate, octyl gallate, lauryl gallate, propyl-hydroxybenzoate, trihydroxybutylrophenone, dimethylphenol, dibutylphenol, vitamin E, lecithin, and ethanolamine; and about 0.0 mg to about 7 mg of a lubricant chosen from calcium stearate, magnesium stearate, zinc stearate, magnesium oleate, calcium palmitate, sodium suberate, potassium laurate, salts of fatty acids, salts of alicyclic acids, salts of aromatic acids, stearic acid, oleic acid, palmitic acid, a mixture of a salt of a fatty, alicyclic, or aromatic acid, and a fatty, alicyclic, or aromatic acid.

In osmotic dosage forms, the semipermeable wall comprises a composition that is permeable to the passage of fluid and impermeable to the passage of prodrug. The wall is nontoxic and comprises a polymer chosen from a cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, and cellulose triacetate. The wall comprises about 75 wt % (weight percent) to about 100 wt % of the cellulosic wall-forming polymer or, the wall may comprise additionally about 0.01 wt % to about 80 wt % of polyethylene glycol, or about 1 wt % to about 25 wt % of a cellulose ether chosen from hydroxypropylcellulose or a hydroxypropylalkycellulose such as hydroxypropylmethylcellulose. The total weight percent of all components comprising the wall is equal to about 100 wt %. The internal compartment comprises the compound-containing composition alone or in layered position with an expandable hydrogel composition. The expandable hydrogel composition in the compartment increases in dimension by imbibing the fluid through the semipermeable wall, causing the hydrogel to expand and occupy space in the compartment, whereby the drug composition is pushed from the dosage form. The therapeutic layer and the expandable layer act together during the operation of the dosage form for the release of prodrug to a patient over time. The dosage form comprises a passageway in the wall that connects the exterior of the dosage form with the internal compartment. The osmotic powered dosage form may be made to deliver prodrug from the dosage form to the patient at a zero order rate of release over a period of up to about 24 hours.

The expression “passageway” as used herein comprises means and methods suitable for the metered release of the compound from the compartment of the dosage form. The exit means comprises at least one passageway, including orifice, bore, aperture, pore, porous element, hollow fiber, capillary tube, channel, porous overlay, or porous element that provides for the osmotic controlled release of compound. The passageway includes a material that erodes or is leached from the wall in a fluid environment of use to produce at least one controlled-release dimensioned passageway. Examples of materials suitable for forming a passageway, or a multiplicity of passageways comprise a leachable poly(glycolic) acid or poly(lactic) acid polymer in the wall, a gelatinous filament, poly(vinyl alcohol), leach-able polysaccharides, salts, and oxides. A pore passageway, or more than one pore passageway, may be formed by leaching a leachable compound, such as sorbitol, from the wall. The passageway possesses controlled-release dimensions, such as round, triangular, square and elliptical, for the metered release of prodrug from the dosage form. The dosage form may be constructed with one or more passageways in spaced apart relationship on a single surface or on more than one surface of the wall. The expression “fluid environment” denotes an aqueous or biological fluid as in a human patient, including the gastrointestinal tract. Passageways and equipment for forming passageways are disclosed in U.S. Pat. Nos. 3,845,770, 3,916,899, 4,063,064, 4,088,864, and 4,816,263. Passageways formed by leaching are disclosed in U.S. Pat. Nos. 4,200,098 and 4,285,987.

Regardless of the specific form of sustained release oral dosage form used, compounds may be released from the dosage form over a period of at least about 6 hours, in certain embodiments, over a period of at least about 8 hours, and in certain embodiments, over a period of at least about 12 hours. Further, the dosage form may release from about 0 to about 30% of the prodrug in about 0 to about 2 hours, from about 20 to about 50% of the prodrug in about 2 to about 12 hours, from about 50 to about 85% of the prodrug in about 3 to about 20 hours, and greater than about 75% of the prodrug in about 5 to about 18 hours. The sustained release oral dosage form further provides a concentration of the 3-aminopropylphosphinic acid analog in the blood plasma of the patient over time, which curve has an area under the curve (AUC) that is proportional to the dose of the prodrug of the 3-aminopropylphosphinic acid analog administered, and a maximum concentration C_max. The C_maxmay be less than about 75%, and in certain embodiments, less than about 60%, of the C_maxobtained from administering an equivalent dose of the compound from an immediate release oral dosage form and the AUC is substantially the same as the AUC obtained from administering an equivalent dose of the prodrug from an immediate release oral dosage form.

In certain embodiments, a pharmaceutical composition or dosage form comprising a compound of Formula (I) is capable of maintaining a therapeutically effective concentration of a compound of Formula (I) in the plasma of a patient for at least about 4 hours, in certain embodiments for at least about 8 hours, and in certain embodiments for at least about 12 hours, after the pharmaceutical composition or dosage form is orally administered to the patient. In certain embodiments, a pharmaceutical composition or dosage form comprising a compound of Formula (I) is capable of maintaining a therapeutically effective concentration of the corresponding 3-aminopropylphosphinc acid or analog thereof of a compound of Formula (I) in the plasma of a patient for at least about 4 hours, in certain embodiments for at least about 8 hours, and in certain embodiments for at least about 12 hours, after the pharmaceutical composition or dosage form is orally administered to the patient. In certain embodiments, dosage forms may be administered once, twice, three times, or four times per day.

Therapeutic Uses of Compounds and Compositions

In certain embodiments, a therapeutically effective amount of one or more compounds of Formula (I) may be administered to a patient, such as a human, suffering from cognitive or memory disorders including Mild Cognitive Impairment (MCI) and cognitive impairment associated with Alzheimer's disease. In certain embodiments, a therapeutically effective amount of one or more compounds of Formula (I) may be administered to a patient, such as a human, suffering from a mood disorder such as depression or anxiety. In certain embodiments, a therapeutically effective amount of one or more compounds of Formula (I) may be administered to a patient, such as a human, suffering from a motion disorder such as epilepsy, particularly “petit-mal” type epilepsy including spontaneous absence epilepsy and atypical absence epilepsy. In certain of the above embodiments, sustained release oral dosage forms are administered to the patients.

When used to treat the diseases or disorders disclosed herein the therapeutically effective amount of one or more compounds of Formula (I) may be administered or applied singly or in combination with other agents. The therapeutically effective amount of one or more compounds of Formula (I) may be capable of delivering a compound disclosed herein in combination with another pharmaceutically active agent, including another compound disclosed herein.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used to treat mood disorders such as depression, or more particularly, depressive disorders, for example, single episodic or recurrent major depressive disorders, dysthymic disorders, depressive neurosis and neurotic depression, melancholic depression, including anorexia, weight loss, insomnia, early morning waking and psychomotor retardation, atypical depression or reactive depression, including increased appetite, hypersomnia, psychomotor agitation or irritability, seasonal affective disorder and pediatric depression; bipolar disorders or manic depression, such as bipolar I disorder, bipolar II disorder, and cyclothymic disorder; conduct disorder and disruptive behavior disorder; anxiety disorders, such as panic disorder with or without agoraphobia, agoraphobia without history of panic disorder, specific phobias, for example, specific animal phobias, social anxiety, social phobia, obsessive-compulsive disorder, stress disorders, including post-traumatic stress disorder and acute stress disorder, and generalized anxiety disorders; borderline personality disorder; schizophrenia and other psychotic disorders, for example, schizophreniform disorders, schizoaffective disorders, delusional disorders, brief psychotic disorders, shared psychotic disorders, psychotic disorders with delusions or hallucinations, psychotic episodes of anxiety, anxiety associated with psychosis, psychotic mood disorders such as severe major depressive disorder; mood disorders associated with psychotic disorders such as acute mania and depression associated with bipolar disorder, mood disorders associated with schizophrenia; and behavioral disturbances associated with mental retardation, autistic disorder, and conduct disorder.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used to treat delirium, dementia, and amnestic and other cognitive or neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, Alzheimer's disease, senile dementia, dementia of the Alzheimer's type, memory disorders including Mild Cognitive Impairment such as occurring after a stroke, in Alzheimer's disease, in delirium, in dementia, or in schizophrenia, loss of executive function, vascular dementia, and other dementias, for example, due to HIV disease, head trauma, Parkinson's disease, Huntington's disease, Pick's disease, Friedrich's disease, Creutzfeldt-Jakob disease, or due to multiple etiologies.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used to treat movement disorders such as akinesias, dyskinesias, including familial paroxysmal dyskinesias, spasticities, Scott syndrome, hiccups, chorea and athetosis, coordination disorders such as Friedrich's ataxia and ataxia-telangiectasia, dystonia including idiopathic torsion dystonia, blepharospasm, spasmodic torticollis, spasmodic dysphonia, yips, and spasmodic torticollis, Huntington's disease, myoclonus, Parkinson's disease, supranuclear palsy, Shy-Drager syndrome, tics including Tourette's syndrome, tremor, and akinetic-rigid syndrome; extra-pyramidal movement disorders such as medication-induced movement disorders, for example, neuroleptic-induced Parkinsonism, neuroleptic malignant syndrome, neuroleptic-induced acute dystonia, neuroleptic-induced acute akathisia, neuroleptic-induced tardive dyskinesia and medication-induced postural tremor.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used to treat chemical dependencies and addictions (e.g., dependencies on, or addictions to, alcohol, heroin, cocaine, benzodiazepines, nicotine, or phenobarbitol) and behavioral addictions such as an addiction to gambling; and ocular disorders such as glaucoma and ischemic retinopathy.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used as an anti-convulsive to treat seizures such as epileptic seizure. Methods for treating convulsions comprise administering a therapeutically effective amount of a 3-aminopropylphosphinic acid analog prodrug of Formula (I) to a patient in need of such treatment. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered orally to treat convulsions and/or seizures. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be parenterally administered to treat convulsions and/or seizures. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered in amounts from about 100 mg to about 4 g daily to treat convulsions and/or seizures.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used as anti-depressants to treat mood disorders such as depression. Methods for treating depression comprise administering a therapeutically effective amount of a 3-aminopropylphosphinic acid analog prodrug of Formula (I) to a patient in need of such treatment. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered orally to treat depression. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be parenterally administered to treat depression. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered in amounts from about 100 mg to about 4 g daily to treat depression.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used to treat mood disorders such as anxiety. Methods for treating anxiety comprise administering a therapeutically effective amount of 3-aminopropylphosphinic acid analog prodrugs of Formula (I) to a patient in need of such treatment. In certain embodiments, a 3-aminopropylphosphinic acid analog prodrug of Formula (I) may be administered orally to treat anxiety. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be parenterally administered to treat anxiety. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered in amounts from about 100 mg to about 4 g daily to treat anxiety.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used to treat cognitive or memory disorders such as cognitive memory impairment and/or cognitive impairment associated with Alzheimer's disease. Methods for treating cognitive memory impairment comprise administering a therapeutically effective amount of a 3-aminopropylphosphinic acid analog prodrug of Formula (I) to a patient in need of such treatment. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered orally to treat cognitive memory disorders. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be parenterally administered to treat cognitive memory disorders. In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered in amounts from about 100 mg to about 4 g daily to treat cognitive memory disorders.

When used to treat and diseases or disorders disclosed herein, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be administered or applied singly, or in combination with other agents. The compounds and/or pharmaceutical compositions comprising a compound of Formula (I) may also be administered or applied singly, or in combination with other pharmaceutically active agents.

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, and/or pharmaceutical compositions thereof may be administered orally. 3-Aminopropylphosphinic acid analog prodrugs of Formula (I) and/or pharmaceutical compositions thereof may also be administered by any other convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal, and intestinal mucosa, etc.). Administration may be systemic or local. Various delivery systems are known, (e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc.) that may be used to administer a compound and/or pharmaceutical composition. Methods of administration include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intranasal, intracerebral, intravaginal, transdermal, rectally, inhalation, or topically, particularly to the ears, nose, eyes, or skin.

In certain embodiments, it may be desirable to introduce 3-aminopropylphosphinic acid analog prodrugs of Formula (I) and/or pharmaceutical compositions thereof into the central nervous system by any suitable route, including intraventricular, intrathecal, and epidural injection. Intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir.

In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) and/or pharmaceutical compositions thereof may be delivered via sustained release systems, may be oral sustained release systems. In other embodiments, a pump may be used (Langer, supra; Sefton, 1987 CRC Crit Ref Biomed Eng. 14, 201; and Saudek et al., 1989 N. Engl. J Med. 321, 574).

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, and/or pharmaceutical compositions thereof may provide therapeutic or prophylactic levels of the corresponding 3-aminopropylphosphinic acid analog upon in vivo administration to a patient. The prodrug promoiety of the compounds of Formula (I) may be cleaved either chemically and/or enzymatically. One or more enzymes present in the stomach, intestinal lumen, intestinal tissue, blood, liver, brain, or any other suitable tissue of a mammal may enzymatically cleave the promoiety of the administered compounds.

The promoiety of a 3-aminopropylphosphinic acid analog prodrug of Formula (I) may be cleaved prior to absorption by the gastrointestinal tract (e.g., within the stomach or intestinal lumen) and/or after absorption by the gastrointestinal tract (e.g., in intestinal tissue, blood, liver, or other suitable tissue of a mammal). In certain embodiments, the 3-aminopropylphosphinic acid analog remains conjugated to the prodrug promoiety during transit across the intestinal mucosal barrier to provide protection from presystemic metabolism. In certain embodiments, a 3-aminopropylphosphinic acid analog prodrugs of Formula (I) is essentially not metabolized to a 3-aminopropylphosphinic acid analog within enterocytes but is metabolized to the parent drug within the systemic circulation. Cleavage of the promoiety of the 3-aminopropylphosphinic acid analog prodrugs of Formula (I) after absorption by the gastrointestinal tract may allow these prodrugs to be absorbed into the systemic circulation either by active transport, passive diffusion, or by a mixture of both active and passive processes. Accordingly, in certain embodiments, a pharmaceutical composition or dosage form of the present disclosure is capable of maintaining a therapeutically effective concentration of a 3-aminopropylphosphinic acid analog compound in the blood plasma of a patient for a period of at least about 4 hours, in certain embodiments for a period of at least about 8 hours, and in certain embodiments for a period of at least about 12 hours, after the pharmaceutical composition or dosage form comprising a corresponding 3-aminopropylphosphinic acid analog prodrug of Formula (I) is orally administered to the patient.

In certain embodiments, prodrugs of 3-aminopropylphosphinic acid analogs provided by the present disclosure can be useful in treating Alzheimer's disease and cognitive or memory disorders associated with Alzheimer's disease. Alzheimer's disease is a progressive loss of mental function characterized by degeneration of brain tissue, including loss of nerve cells and the development of senile plaques and neurofibrillary tangles. In Alzheimer's disease, parts of the brain degenerate, destroying nerve cells and reducing the responsiveness of the maintaining neurons to neurotransmitters. Abnormalities in brain tissue consist of senile or neuritic plaques, e.g., clumps of dead nerve cells containing an abnormal, insoluble protein called amyloid, and neurofibrillary tangles, twisted strands of insoluble proteins in the nerve cell.

The efficacy of administering a prodrug of a 3-aminopropylphosphinic acid analog provided by the present disclosure for treating Alzheimer's disease may be assessed using animal and human models of Alzheimer's disease and clinical studies. Useful animal models for assessing the efficacy of compounds for treating Alzheimer's disease are disclosed, for example, in Van Dam and De Dyn, Nature Revs Drug Disc 2006, 5, 956-970; Simpkins et al., Ann N Y Acad Sci, 2005, 1052, 233-242; Higgins and Jacobsen, Behav Pharmacol 2003, 14(5-6), 419-38; Janus and Westaway, Physiol Behav 2001, 73(5), 873-86; Bardgett et al., Brain Res Bull 2003, 60, 131-142; and Conn, ed., “Handbook of Models in Human Aging,” 2006, Elsevier Science & Technology.

In certain embodiments, compounds prodrugs of 3-aminopropylphosphinic acid analogs provided by the present disclosure and pharmaceutical compositions thereof can be used to treat a mood disorder such as, for example, a bipolar disorder and a depressive disorder.

Bipolar disorder is a psychiatric condition characterized by periods of extreme mood. The moods can occur on a spectrum ranging from depression (e.g., persistent feelings of sadness, anxiety, built, anger, isolation, and/or hopelessness, disturbances in sleep and appetite, fatigue and loss of interest in usually enjoyed activities, problems concentrating, loneliness, self-loathing, apathy or indifference, depersonalization, loss of interest in sexual activity, shyness or social anxiety, irritability, chronic pain, lack of motivation, and morbid/suicidal ideation) to mania (e.g., elation, euphoria, irritation, and/or suspicious). Bipolar disorder is defined and classified in DSM-IV-TR. Bipolar disorder includes bipolar I disorder, bipolar II disorder, cyclothymia, and bipolar disorder not otherwise specified. Bipolar disorder is a common, severe, chronic and one of the most debilitating of all medical illnesses. Patients afflicted with this disorder typically alternate between episodes of depression (depressed mood, hopelessness, anhedonia, varying sleep disturbances, difficulty in concentration, psychomotor retardation and often, suicidal ideation) and episodes of mania (grandiosity, euphoria, racing thoughts, decreased need for sleep, increased energy, risk taking behavior).

Treatment of bipolar disorder can be assessed in clinical trials using rating scales such as the Montgomery-Asberg Depression Rating Scale, the Hamilton Depression Scale, the Raskin Depression Scale, Feighner criteria, and/or Clinical Global Impression Scale Score (Gijsman et al., Am J Psychiatry 2004, 161, 1537-1547; and Post et al., J Clin Psychiatry 2005, 66(3), 370-374).

Depressive disorders include major depressive disorder, dysthymic disorder, premenstrual dysphoric disorder, minor depressive disorder, recurrent brief depressive disorder, and postpsychotic depressive disorder of schizophrenia (see DSM IV).

The efficacy of compounds provided by the present disclosure for treating depression can be evaluated in animal models of depression such as the forced swim test (Porsolt et al., Nature 1977, 266, 525-532; and Porsolt et al., Arch Int Pharmacodyn 1997, 229, 327-336), the tail suspension test (Cryan et al., Trends Pharmacol Sci 2002, 23, 238-245; and Cryan and Mombereau, Mol Psychiatr 2004, 9, 1050-1062), and well as other (Porsolt, Rev. Neurosci 2000, 11, 53-58).

In certain embodiments, prodrugs of 3-aminopropylphosphinic acid analogs provided by the present disclosure can be useful in treating anxiety. Anxiety is defined and classified in DSM-IV-TR. Anxiety disorders include panic attack, agoraphobia, panic disorder without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, posttraumatic stress disorder, acute stress disorder, generalized anxiety disorder, anxiety disorder due to a general medical condition, substance-induced anxiety disorder, and anxiety disorder not otherwise specified.

Useful animal models for assessing treatment of anxiety include fear-potentiated startle (Brown et al., J Experimental Psychol 1951, 41, 317-327); elevated plus-maze (Pellow et al., J Neurosci. Methods 1985, 14, 149-167; and Hogg, Pharmacol Biochem Behavior 1996, 54(1), 21-20); fear-potentiated behavior in the elevated plus-maze test (Korte and De Boer, Eur J Pharmacol 2003, 463, 163-175); X-maze test of anxiety (Handley and Mithani, Arch Pharmacol 1984, 327, 1-5); and rat social interaction test (File, J Neurosci Methods 1980, 2, 219-238). Genetic animal models of anxiety are known (Toh, Eur J Pharmacol 2003, 463, 177-184) as are other animal models sensitive to anti-anxiety agents (Martin, Acta Psychiatr Scand 1998, Suppl 393, 74-80).

In clinical trials, efficacy can be evaluated using psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders (see e.g., Graeff, et al., Brazilian J Medical Biological Res 2003, 36, 421-32) or by selecting patients based on the Structured Clinical interview for DSM-IV Axis I Disorders as described by First et al., Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCIDIP), Version 2. Biometrics Research, New York State Psychiatric Institute, New York, 1995. One or more scales can be used to evaluate anxiety and the efficacy of treatment including, for example, the Penn State Worry Questionnaire (Behar et al., J Behav Ther Exp Psychiatry 2003, 34, 25-43), the Hamilton Anxiety and Depression Scales, the Spielberger State-Trait Anxiety Inventory, and the Liebowitz Social Anxiety Scale (Hamilton, J Clin Psychiatry 1980, 41, 21-24; Spielberger and Vagg, J Personality Assess 1984, 48, 95-97; and Liebowitz, J Clin Psychiatry 1993, 51, 31-35 (Suppl)).

In certain embodiments, prodrugs of 3-aminopropylphosphinic acid analogs provided by the present disclosure can be useful in treating seizure disorders such as epilepsy. Seizure disorders such as epilepsy involve periodic disturbances of the brain's electrical activity, resulting in some degree of temporary brain dysfunction. Seizures can be localized (partial or focal onset seizures) or distributed (generalized seizures). Partial seizures can be simple, in which a person is completely conscious and aware of the surroundings, or complex, in which consciousness is impaired but not completely lost. Partial seizures include simple partial seizures, Jacksonian seizures, complex partial seizures, and epilepsia partialis continua. Generalized seizures cause a loss of consciousness and abnormal movements. Generalized seizures include tonic-clonic seizures, primary generalized epilepsy, bsence seizures, atonic seizures, myoclonic seizures, and status epilepticus.

GABA_Bantagonists are also useful in the treatment of epilepsy, particularly “petit-mal” type epilepsy, including spontaneous absence epilepsy and atypical absence epilepsy (see e.g., Marescaux et al., U.S. Pat. No. 5,407,922; Marescaux et al., U.S. Pat. No. 5,545,631; Czuczwar and Patsalos, CNS Drugs, 2001, 15, 339-350; Getova et al., Eur. J. Pharmacol. 1997, 320, 9-13; Vergnes et al., Eur. J. Pharmacol. 1997, 332, 245-255; and Marescaux et al., J. Neural Transm. 1992, 35, 179-188).

Animal models that are useful for evaluating the efficacy of compounds for treating seizure disorders are known (see, e.g., Murashima et al, Epilepsia 2002, 43(Suppl. 5), 130-135; and Kudin et al., Eur J Neurosci 2002, 15, 1105-14)).

Doses

3-Aminopropylphosphinic acid analog prodrugs of Formula (I) may be administered to treat diseases or disorders such as mild cognitive impairment, cognitive impairment associated with Alzheimer's disease, depression, anxiety, epilepsy, and others disclosed herein.

The amount of 3-aminopropylphosphinic acid analog prodrugs of Formula (I) that will be effective in the treatment of a particular disorder or condition disclosed herein will depend on the nature of the disorder or condition, and may be determined by standard clinical techniques known in the art. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. The amount of a compound administered will, of course, be dependent on, among other factors, the subject being treated, the weight of the subject, the severity of the affliction, the manner of administration, and the judgment of the prescribing physician.

In certain embodiments, the dosage forms are adapted to be administered to a patient no more than twice per day, and in certain embodiments, only once per day. Dosing may be provided alone or in combination with other drugs and may continue as long as required for effective treatment of the disease state or disorder.

Suitable dosage ranges for oral administration are dependent on the potency of the parent 3-aminopropylphosphinic acid analog. For certain 3-aminopropylphosphinic acid analogs, doses are generally between about 0.1 mg to about 20 mg per kilogram body weight. Other 3-aminopropylphosphinic acid analogs may be more potent and lower doses may be appropriate for both the parent drug and any prodrug (measured on an equivalent molar basis). Dosage ranges may be readily determined by methods known to the skilled artisan.

Combination Therapy

In certain embodiments, 3-aminopropylphosphinic acid analog prodrugs of Formula (I) or pharmaceutically acceptable salts or solvates thereof as disclosed herein, may be used in combination therapy with at least one other therapeutic agent. 3-Aminopropylphosphinic acid analog prodrugs of Formula (I) and the other therapeutic agent(s) may act additively or, and in certain embodiments, synergistically. In certain embodiments, a 3-aminopropylphosphinic acid analog prodrug of Formula (I) may be administered concurrently with the administration of another therapeutic agent, such as for example, an anti-depressant, anxiolytic, sedative, non-steroidal anti-inflammatory drug, selective serotonin reuptake inhibitor, monoamine oxidase inhibitor, psychostimulant, antipsychotic, anticonvulsant, or sedative. In certain embodiments, a 3-aminopropylphosphinic acid analog prodrug of Formula (I) or pharmaceutically acceptable salts or solvates thereof may be administered prior or subsequent to administration of another therapeutic agent, such as for example, an antidepressant, anxiolytic, sedative, non-steroidal anti-inflammatory drug, selective serotonin reuptake inhibitor, monoamine oxidase inhibitor, psychostimulant, antipsychotic, or anticonvulsant.

Pharmaceutical compositions of the present disclosure may include, in addition to one or more compounds of the present disclosure, one or more therapeutic agents effective for treating the same or different disease, disorder, or condition.

Methods of the present disclosure include administration of one or more compounds or pharmaceutical compositions of the present disclosure and one or more other therapeutic agents provided that the combined administration does not inhibit the therapeutic efficacy of the one or more compounds of the present disclosure and/or does not produce adverse combination effects.

In certain embodiments, compositions of the present disclosure may be administered concurrently with the administration of another therapeutic agent, which may be part of the same pharmaceutical composition as, or in a different composition from, that containing the compounds of the present disclosure. In certain embodiments, compounds of the present disclosure may be administered prior or subsequent to administration of another therapeutic agent. In certain embodiments of combination therapy, the combination therapy comprises alternating between administering a composition of the present disclosure and a composition comprising another therapeutic agent, e.g., to minimize adverse side effects associated with a particular drug. When a compound of the present disclosure is administered concurrently with another therapeutic agent that potentially may produce adverse side effects including, but not limited to, toxicity, the therapeutic agent may advantageously be administered at a dose that falls below the threshold at which the adverse side effect is elicited.

In certain embodiments, a drug may further comprise substances to enhance, modulate and/or control release, bioavailability, therapeutic efficacy, therapeutic potency, stability, and the like. For example, to enhance therapeutic efficacy a drug may be co-administered with one or more active agents to increase the absorption or diffusion of the drug from the gastrointestinal tract, or to inhibit degradation of the drug in the systemic circulation. In certain embodiments, a drug may be co-administered with active agents having pharmacological effects that enhance the therapeutic efficacy of the drug.

In certain embodiments, compounds or pharmaceutical compositions of the present disclosure include, or may be administered to a patient together with, another compound for treating anxiety, drugs for treating seizure disorders such as epilepsy, drugs for treating cognitive or memory disorders, or drugs for treating depression.

Examples of drugs for treating mood disorders such as anxiety include benzodiazepines such as alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, and oxazepam; antidepressants including tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, and trimipramine, selective serotonin reuptake inhibitors such as citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; monoamine oxidase inhibitors such as phenelzine and tranylcypromine, and other antidepressants such as bupropion, mirtazapine, nefazodone, trazodone, and venlafaxine; and other anxiolytics such as hydroxyzine, mecloqualone, medetomidine, metomidate, adinazolam, chlordiazepoxide, clobenzepam, flurazepam, lorazepam, loprazolam, midazolam, alpidem, alseroxlon, amphenidone, azacyclonol, bromisovalum, captodiamine, capuride, carbcloral, carbromal, chloralbetaine, enciprazine, flesinoxan, ipsapiraone, lesopitron, loxapine, methaqualone, methprylon, propanolol, tandospirone, trazadone, zopiclone, and zolpidem.

Examples of drugs for treating mood disorders such as depression include tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, and trimipramine; selective serotonin reuptake inhibitors such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; serotonin-noradrenaline reuptake inhibitors such as venlafaxine, duloxetine, sibutramine, and milnacipran; monoamine oxidase inhibitors such as phenelzine and tranylcypromine; and psychostimulants such as dextroamphetamine and methylphenidate. Other antidepressants include benmoxine, butriptyline, dosulepin, imipramine, kitanserin, lofepramine, medifoxamine, mianserin, mirtazapine, viloxazine, cotinine, nisoxetine, reboxetine, tianeptine, acetaphenazine, binedaline, brofaromine, cericlamine, clovoxamine, iproniazid, isocarboxazid, moclobemide, phenyhydrazine, selegiline, sibutramine, ademetionine, adrafinil, amesergide, amisulpride, amperozide, benactyzine, bupropion, caroxazone, gepirone, idazoxan, metralindole, minaprine, nefazodone, nomifensine, ritanserin, roxindole, S-adenosylmethionine, escitalopram, tofenacin, trazodone, tryptophan, zalospirone, and Saint John's wort. Compounds and compositions of the present disclosure may also be used in conjunction with psychotherapy or electroconvulsive therapy to treat mood disorders such as depression.

Examples of drugs for treating seizures such as epilepsy include anticonvulsants such as carbamazepine, clonazepam, divalproex, ethosuximide, felbamate, fosphenyloin, gabapentin, lamotrigine, levetiracetam, lorazepam, midazolam, oxcarbazepine, phenobarbital, phenyloin, primidone, tiagabine, topiramate, valproic acid, vigabatrin, and zonisamide; and sedatives such as diazepam and lorazepam.

Examples of drugs for treating cognitive or memory disorders include antipsychotic drugs such as chlorpromazine, fluphenazine, haloperidol, loxapine, mesoridazine, molindone, perphenazine, pimozide, thioridazine, thiothixene, trifluoperazine, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone; sedatives such as diazepam and lorazepam; benzodiazepines such as alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, and oxazepam; nonsteroidal anti-inflammatory drugs such as aceclofenac, acetaminophen, alminoprofen, amfenac, aminopropylon, amixetrine, aspirin, benoxaprofen, bromfenac, bufexamac, carprofen, celecoxib, choline, salicylate, cinchophen, cinmetacin, clopriac, clometacin, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, indoprofen, ketoprofen, ketorolac, mazipredone, meclofenamate, nabumetone, naproxen, parecoxib, piroxicam, pirprofen, rofecoxib, sulindac, tolfenamate, tolmetin, and valdecoxib; acetylcholinesterase inhibitors such as donepezil, galantamine, rivastigmine, physostigmine, and tacrine; or N-methyl-D-aspartate (NMDA) receptor blockers such as memantine.

EXAMPLES

The following examples describe in detail preparation of compounds disclosed herein. It will be apparent to those of ordinary skill in the art that many modifications, both to materials and methods, may be practiced.

In the examples below, the following abbreviations have the following meanings. If an abbreviation is not defined, it has its generally accepted meaning.

Atm=atmosphere

Boc=tert-butyloxycarbonyl

Cbz=carbobenzyloxy

DCC=dicyclohexylcarbodiimide

DMAP=4-N,N-dimethylaminopyridine

DMF=N,N-dimethylformamide

DMSO=dimethylsulfoxide

g=gram

h=hour

HPLC=high pressure liquid chromatography

L=liter

LC/MS=liquid chromatography/mass spectroscopy

M=molar

min=minute

mL=milliliter

mmol=millimoles

NHS=N-hydroxysuccinimide

THF=tetrahydrofuran

TFA=trifluoroacetic acid

TLC=thin layer chromatography

TMS=trimethylsilyl

μL=microliter

μM=micromolar

v/v=volume to volume

Synthesis of Chemical Intermediates Useful in Synthesizing Acyloxyalkyl Carbamate Prodrugs of 3-Aminopropylphosphinic Acid

O-(1-Isobutanoyloxyethyl) S-methyl thiocarbonate (2) was synthesized using a two-step process. In a first step (Step A), a 21% (w/w) aqueous solution of sodium methylthiolate (580.7 g, 1.74 mol) was added to a solution of 1-chloroethyl chloroformate (250 g, 1.74 mol) and tetrabutylammonium hydrogensulfate (5.9 g, 17 mmol) in CH₂Cl₂(450 mL) over 2 h. The reaction mixture was stirred for an additional hour, then worked-up by separating the aqueous phase and extracting the organic phase with brine (2×250 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by vacuum distillation to afford O-(1-chloroethyl) S-methyl thiocarbonate (3) as a colorless liquid (277.3 g, 97% yield). ¹H NMR (CDCl₃, 400 MHz): δ 1.82 (d, J=5.6 Hz, 3H), 2.38 (s, 3H), 6.57 (q, J=5.2 Hz, 1H).

In a second step (Step B), compound (3) (308 g, 2 mol) was dissolved in isobutyric acid (264 g, 3 mol). This mixture was slowly added to a pre-mixed solution of isobutyric acid (264 g, 3 mol) and diisopropylethylamine (387 g, 3 mol), and the reaction mixture heated to 55° C. for 16 h, diluted with ether (10 L), washed with water (4×5 L), saturated bicarbonate solution (2×5 L) and brine (5 L), then dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give compound (2) as a colorless liquid (400 g, 97% yield). The product was optionally further purified by vacuum distillation (135° C./20 Torr). ¹H NMR (CDCl₃, 400 MHz): δ1.17 (d, J=6.8 Hz, 6H), 1.49 (d, J=5.6 Hz, 3H), 2.33 (s, 3H), 2.54 (m, 1H), 6.91 (q, J=5.2 Hz, 1H).

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing isobutyric acid with n-butyric acid in Step B affords O-(1-butanoyloxyethyl) S-methyl thiocarbonate (4) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing isobutyric acid with pivalic acid in Step B affords O-(1-pivaloyloxyethyl) S-methyl thiocarbonate (5) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing isobutyric acid with cyclohexanecarboxylic acid in Step B affords O-(cyclohexylethyl) S-methyl thiocarbonate (6) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing isobutyric acid with benzoic acid in Step B affords O-(benzoyloxyethyl) S-methyl thiocarbonate (215) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing 1-chloroethyl chloroformate with chloromethyl chloroformate in Step A affords O-(isobutanoyloxymethyl) S-methyl thiocarbonate (7) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing 1-chloroethyl chloroformate with chloromethyl chloroformate in Step A and replacing isobutyric acid with n-butyric acid in Step B affords O-(butanoyloxymethyl) S-methyl thiocarbonate (8) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing 1-chloroethyl chloroformate with chloromethyl chloroformate in Step A and replacing isobutyric acid with pivalic acid in Step B affords O-(pivaloyloxymethyl) S-methyl thiocarbonate (9) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing 1-chloroethyl chloroformate with chloromethyl chloroformate in Step A and replacing isobutyric acid with cyclohexanecarboxylic acid in Step B affords O-(cyclohexanoyloxymethyl) S-methyl thiocarbonate (10) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyethyl) S-methyl thiocarbonate (2) and replacing 1-chloroethyl chloroformate with chloromethyl chloroformate in Step A and replacing isobutyric acid with benzoic acid in Step B affords O-(benzoyloxymethyl) S-methyl thiocarbonate (213) as an oil.

O-(1-Isobutanoyloxyisobutoxy) S-methyl thiocarbonate (11) was synthesized in a three-step process. In a first step (Step A), a solution of 1-chloro-2-methylpropyl chloroformate (1026 g, 6.0 mol) and tetrabutylammonium hydrogensulfate (20 g, 60 mmol) in dichloromethane (1500 mL) in a jacketed 10 L reactor equipped with a mechanical stirrer, temperature probe, and addition funnel was cooled to 10° C. To the reaction mixture was gradually added a 15% aqueous solution of sodium methylthiolate (3 L, 6.4 mol) over 4 h. The reaction was moderately exothermic and the internal temperature was maintained between 10 and 20° C. during the addition. The aqueous phase was separated and the organic phase was washed with brine (2×2 L) and water (2 L). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to afford O-(1-chloroisobutoxy) S-methyl thiocarbonate (12) (1050 g, 5.76 mol, 96% yield) as a colorless liquid. ¹H NMR (CDCl₃, 400 MHz): δ 1.1 (dd, 6H), 2.2 (m, 1H), 2.4 (s, 3H), 6.35 (d, 1H).

In a second step (Step B), to a 20 L round bottom flask was added isobutyric acid (1300 mL, 14 mol), and an aqueous solution of 25% tetramethylammonium hydroxide (5 L, 14 mol). The water was removed under reduced pressure, and azeotroped with toluene (2×2 L) to leave tetramethylammonium isobutyrate (13) as an amber liquid, which was used without further purification.

In a third step (Step C), to a 3 L three neck round bottom flask equipped with a mechanical stirrer and Teflon-coated thermocouple was added compound (13) (1672 g, 9 mol), isobutyric acid (264 g, 1.5 mol), and compound (12) (1050 g, 5.76 mol). The reaction mixture was heated to 80° C. for 12 h, monitoring the reaction progress by ¹H NMR. The reaction mixture was cooled to 20° C., diluted with EtOAc (1 L) and washed with water (2×1 L), saturated NaHCO₃(1×2 L) and water (1 L). The organic phase was separated and concentrated under reduced pressure to afford O-(1-isobutanoyloxyisobutoxy) S-methyl thiocarbonate (11) (905 g, 3.9 mol, 65%) as a colorless liquid. ¹H NMR (CDCl₃, 400 MHz): δ 1.0 (d, 6H), 1.2 (dd, 6H), 2.05 (m, 1H), 2.35 (s, 3H), 2.6 (m, 1H), 6.7 (d, 1H).

Following the procedures for synthesizing O-(1-isobutanoyloxyisobutoxy) S-methyl thiocarbonate (11) and replacing isobutyric acid with n-butyric acid affords O-(1-butanoyloxyisobutoxy) S-methyl thiocarbonate (14) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyisobutoxy) S-methyl thiocarbonate (11) and replacing isobutyric acid with pivalic acid affords O-(1-pivaloyloxyisobutoxy) S-methyl thiocarbonate (15) as an oil.

Following the procedures for synthesizing O-(1-isobutanoyloxyisobutoxy) S-methyl thiocarbonate (11) and replacing isobutyric acid with cyclohexanecarboxylic acid affords O-(1-cyclohexanoyloxyisobutoxy) S-methyl thiocarbonate (16) as an oil.

[(1-Isobutanoyloxyethoxy)carbonyloxy]succinimide (17) was synthesized using the following procedure. To a solution of compound (2) (1 g, 4.8 mmol) in CH₂Cl₂(10 mL) was added N-hydroxysuccinimide (1.1 g, 9.5 mmol) and the reaction mixture cooled to 0° C. A solution of 32% (v/v) peracetic acid in acetic acid (3.4 mL, 1.1 g, 14.4 mmol) was added dropwise over a period of 10 min, then the solution allowed to stir at room temperature for 3 h. The reaction mixture was diluted with ether (50 mL) and washed with water (2×10 mL), saturated sodium bicarbonate solution (10 mL) and brine (10 mL), then dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give compound (17) as a as colorless oil (1 g, 77% yield). After trituration with hexane (20 mL) the product solidified to a white solid. m.p: 50-54° C. ¹H NMR (CDCl₃, 400 MHz): δ1.17 (d, J=6.8 Hz, 6H), 1.56 (d, J=5.6 Hz, 3H), 2.55 (m, 1H), 2.82 (s, 4H), 6.80 (q, J=5.2 Hz, 1H). MS (ESI) m/z 296.4 (M+Na)⁺.

Following the procedures for synthesizing [(1-isobutanoyloxyethoxy)carbonyloxy]succinimide (17) and replacing compound (2) with compound (4) affords [(1-butanoyloxyethoxy)carbonyloxy]succinimide (18).

Following the procedures for synthesizing [(1-isobutanoyloxyethoxy)carbonyloxy]succinimide (17) and replacing compound (2) with compound (5) affords [(1-pivaloyloxyethoxy)carbonyloxy]succinimide (19).

Following the procedures for synthesizing [(1-isobutanoyloxyethoxy)carbonyloxy]succinimide (17) and replacing compound (2) with compound (6) affords [(1-cyclohexanoyloxyethoxy)carbonyloxy]succinimide (20).