ISOINDOLINONES, PHARMACEUTICAL COMPOSITIONS, AND THERAPEUTIC APPLICATIONS

Description

FIELD

Provided herein are isoindolinones and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a zinc-figure protein, casein kinase 1α, GSPT1, or PDE6D.

BACKGROUND

Molecular glues are monovalent compounds that bind simultaneously two distinct proteins, e.g., a ubiquitin ligase and a target protein, leading to the ubiquitination and subsequent proteasome-based degradation of the target protein. Schreiber Cell 2020, 184, 3-9; Kozicka and Thoma, Cell Chem. Biol. 2021, 28, 1032-47; Faust et al., Ann. Rev. Cancer Biol. 2021, 5, 181-201. Revlimid (lenalidomide), one of the most successful anticancer drugs, is a molecular glue. Kronke et al., Science 2014, 343, 301-5. Molecular glues have several advantages over traditional small-molecule enzyme inhibitors or receptor antagonists. Dong et al., J. Med. Chem. 2021, 64, 10606-20. Mechanistically, molecular glues drive target ubiquitination and degradation in a substoichiometric and catalytic manner. Id. As they do not require a druggable pocket on the target protein, molecular glues are able to degrade a therapeutic target that is intractable by conventional approaches. Id.

Molecular glues are distinctly different from proteolysis targeting chimeras (PROTACs). While PROTACs are bifunctional molecules—chimeras having two moieties connected together by a linker, molecular glues are monovalent small molecules that act as adhesives to bring two proteins together. These linker-based bifunctional PROTACs generally have high molecular weight (MW), poor cellular permeability, and unfavorable pharmacokinetic (PK) profiles. Edmondson et al., Bioorg. Med. Chem. Lett. 2019, 29, 1555-64. The physicochemical properties of molecular glues are similar to those of traditional small-molecule drugs. Thus, molecular glues generally possess more favorable drug-like properties, such as lower MW, higher cell permeability, and better oral absorption. Therefore, molecular glues offer an attractive approach to drug discovery in targeted protein degradation.

SUMMARY OF THE DISCLOSURE

Provided herein is a compound of Formula (I):

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or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:

- R¹is hydrogen, deuterium, or C_1-6alkyl;
- R²is hydrogen or C_1-6alkyl;
- R³and R⁴are:
- (i) R³is halo; and
  - R⁴is

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- - or
- (ii) R³is hydrogen, deuterium, or halo; and
  - R⁴is

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- each R⁵is independently (i) deuterium, cyano, halo, or nitro; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) —C(O)R^1a, —C(O)OR^1a, —C(O)NR^1bR^1c, —C(O)SR^1a, —C(NR^1a)NR^1bR^1c, —C(S)R^1a, —C(S)OR^1a, —C(S)NR^1bR^1c, —OR^1a, —OC(O)R^1a, —OC(O)OR^1a, —OC(O)NR^1bR^1c, —OC(O)SR^1a, —OC(NR^1a)NR^1bR^1c, —OC(S)R^1a, —OC(S)OR^1a, —OC(S)NR^1bR^1c, —OS(O)R^1a, —OS(O)₂R^1a, —OS(O)NR^1bR^1c, —OS(O)₂NR^1bR^1c, —R^1bR^1c, —NR^1aC(O)R^1d, —NR^1aC(O)OR^1d, —NR^1aC(O)NR^1bR^1c, —NR^1aC(O)SR^1d, —NR^1aC(NR^1d)NR^1bR^1c, —NR^1aC(S)R^1d, —NR^1aC(S)OR^1d, —NR^1aC(S)NR^1bR^1c, —NR^1aS(O)R^1d, —NR^1aS(O)₂R^1d, —NR^1aS(O)NR^1bR^1c, —NR^1aS(O)₂NR^1bR^1c, —SR^1a, —S(O)R^1a, —S(O)₂R^1a, —S(O)NR^1bR^1c, or —S(O)₂NR^1bR^1c;
- each R⁶is independently C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl;
- each R^1a, R^1b, R^1c, and R^1dis independently hydrogen, deuterium, C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl;
- each A is independently CR^4aor N; wherein R^4ais hydrogen, deuterium, halo, C_1-6alkyl, or C_1-6heteroalkyl;
- each X is independently —(CH₂)_n—, —C(O)—, —S(O)—, or —S(O₂)—; wherein n is an integer of 1, 2, 3, 4, or 5;
- each a, b, c, d, e, and f is independently an integer of 0, 1, 2, or 3; and
- m is an integer of 0, 1, 2, or 3;
- wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, and heterocyclyl is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; and (c) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —C(O)SR^a, —C(NR^a)NR^bR^c, —C(S)R^a, —C(S)OR^a, —C(S)NR^bR^c, —OR^a, —OC(O)R^a, —OC(O)OR^a, —OC(O)NR^bR^c, —OC(O)SR^a, —OC(NR^a)NR^bR^c, —OC(S)R^a, —OC(S)OR^a, —OC(S)NR^bR^c, —OP(O)(OR^b)OR^c, —OS(O)R^a, —OS(O)₂R^a, —OS(O)NR^bR^c, —OS(O)₂NR^bR^c, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aC(O)NR^bR^c, —NR^aC(O)SR^d, —NR^aC(NR^d)NR^b, —NR^aC(S)R^d, —NR^aC(S)OR^d, —NR^aC(S)NR^bR^c, —NR^aS(O)R^d, —NR^aS(O)₂R^d, —NR^aS(O)NR^bR^c, —NR^aS(O)₂NR^bR^c, —SR^a, —S(O)R^a, —S(O)₂R^a, —S(O)NR^bR^c, and —S(O)₂NR^bR^c, wherein each R^a, R^b, R^c, and R^dis independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; or (iii) R^band R^ctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a;
- wherein each Q^ais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, and heterocyclyl; and (c) —C(O)R^e, —C(O)OR^e, —C(O)NR^fR^g, —C(O)SR^e, —C(NR^e)NR^fR^g, —C(S)R^e, —C(S)OR^e, —C(S)NR^fR^g, —OR^e, —OC(O)R^e, —OC(O)OR^e, —OC(O)NR^fR^g, —OC(O)SR^e, —OC(NR^e)NR^fR^g, —OC(S)R^e, —OC(S)OR^e, —OC(S)NR^fR^g, —OP(O)(OR^f)OR^g, —OS(O)R^e, —OS(O)₂R^e, —OS(O)NR^fR^g, —OS(O)₂NR^fR^g, —NR^fR^g, —NR^eC(O)R^h, —NR^eC(O)OR^f, —NR^eC(O)NR^fR^g, —NR^eC(O)SR^f, —NR^eC(NR^h)NR^fR^g, —NR^eC(S)R^h, —NR^eC(S)OR^f, —NR^eC(S)NR^fR^g, —NR^eS(O)R^h, —NR^eS(O)₂R^h, —NR^eS(O)NR^fR^g, —NR^eS(O)₂NR^fR^g, —SR^e, —S(O)R^e, —S(O)₂R^e, —S(O)NR^fR^g, and —S(O)₂NR^fR^g; wherein each R^e, R^f, R^g, and R^his independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) R^fand R^gtogether with the N atom to which they are attached form heterocyclyl.

Also provided herein is a pharmaceutical composition comprising a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; and a pharmaceutically acceptable excipient.

Additionally, provided herein is a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a zinc-figure protein, CK1α, GSPT1, and/or PDE6D in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

Furthermore provided herein is a method of treating, preventing, or ameliorating one or more symptoms of a proliferative disease in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

Provided herein is a method of inhibiting the growth of a cell, comprising contacting the cell with an effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

Provided herein is a method of inducing degradation of a protein, comprising contacting the protein with an effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof, wherein the protein is a zinc-figure protein, CK1α, GSPT1, or PDE6D.

DETAILED DESCRIPTION

To facilitate understanding of the disclosure set forth herein, a number of terms are defined below.

Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, biochemistry, biology, and pharmacology described herein are those well-known and commonly employed in the art. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

The term “subject” refers to an animal, including, but not limited to, a primate (e.g., human), cow, pig, sheep, goat, horse, dog, cat, rabbit, rat, or mouse. The terms “subject” and “patient” are used interchangeably herein in reference, for example, to a mammalian subject, such as a human subject. In one embodiment, the subject is a human.

The terms “treat,” “treating,” and “treatment” are meant to include alleviating or abrogating a disorder, disease, or condition, or one or more of the symptoms associated with the disorder, disease, or condition; or alleviating or eradicating the cause(s) of the disorder, disease, or condition itself.

The terms “prevent,” “preventing,” and “prevention” are meant to include a method of delaying and/or precluding the onset of a disorder, disease, or condition, and/or its attendant symptoms; barring a subject from acquiring a disorder, disease, or condition; or reducing a subject's risk of acquiring a disorder, disease, or condition.

The terms “alleviate” and “alleviating” refer to easing or reducing one or more symptoms (e.g., pain) of a disorder, disease, or condition. The terms can also refer to reducing adverse effects associated with an active ingredient. Sometimes, the beneficial effects that a subject derives from a prophylactic or therapeutic agent do not result in a cure of the disorder, disease, or condition.

The term “contacting” or “contact” is meant to refer to bringing together of a therapeutic agent and a biological molecule (e.g., a protein, enzyme, RNA, or DNA), cell, or tissue such that a physiological and/or chemical effect takes place as a result of such contact. Contacting can take place in vitro, ex vivo, or in vivo. In one embodiment, a therapeutic agent is contacted with a biological molecule in vitro to determine the effect of the therapeutic agent on the biological molecule. In another embodiment, a therapeutic agent is contacted with a cell in cell culture (in vitro) to determine the effect of the therapeutic agent on the cell. In yet another embodiment, the contacting of a therapeutic agent with a biological molecule, cell, or tissue includes the administration of a therapeutic agent to a subject having the biological molecule, cell, or tissue to be contacted.

The term “therapeutically effective amount” or “effective amount” is meant to include the amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more of the symptoms of the disorder, disease, or condition being treated. The term “therapeutically effective amount” or “effective amount” also refers to the amount of a compound that is sufficient to elicit a biological or medical response of a biological molecule (e.g., a protein, enzyme, RNA, or DNA), cell, tissue, system, animal, or human, which is being sought by a researcher, veterinarian, medical doctor, or clinician.

The term “IC₅₀” or “EC₅₀” refers to an amount, concentration, or dosage of a compound that is required for 50% inhibition of a maximal response in an assay that measures such a response.

The term “pharmaceutically acceptable carrier,” “pharmaceutically acceptable excipient,” “physiologically acceptable carrier,” or “physiologically acceptable excipient” refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material. In one embodiment, each component is “pharmaceutically acceptable” in the sense of being compatible with the other ingredients of a pharmaceutical formulation, and suitable for use in contact with the tissue or organ of a subject (e.g., a human) without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, and commensurate with a reasonable benefit/risk ratio. See, e.g., Remington: The Science and Practice of Pharmacy, 23rd ed.; Adejare Ed.; Academic Press, 2020; Handbook of Pharmaceutical Excipients, 9th ed.; Sheskey et al., Eds.; Pharmaceutical Press, 2020; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Synapse Information Resources, 2007; Pharmaceutical Preformulation and Formulation, 1st ed.; Gibson Ed.; CRC Press, 2015.

The term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. In certain embodiments, the term “about” or “approximately” means within 1, 2, or 3 standard deviations. In certain embodiments, the term “about” or “approximately” means within 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range.

The term “alkyl” refers to a linear or branched saturated monovalent hydrocarbon radical, wherein the alkyl is optionally substituted with one or more substituents Q as described herein. For example, C_1-6alkyl refers to a linear saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (C_1-20), 1 to 15 (C_1-15), 1 to 10 (C_1-10), or 1 to 6 (C_1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20 (C_3-20), 3 to 15 (C_3-15), 3 to 10 (C_3-10), or 3 to 6 (C_3-6) carbon atoms. As used herein, linear C_1-6and branched C_3-6alkyl groups are also referred as “lower alkyl.” Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including all isomeric forms, e.g., n-propyl and isopropyl), butyl (including all isomeric forms, e.g., n-butyl, isobutyl, sec-butyl, and t-butyl), pentyl (including all isomeric forms, e.g., n-pentyl, isopentyl, sec-pentyl, neopentyl, and tert-pentyl), and hexyl (including all isomeric forms, e.g., n-hexyl, isohexyl, and sec-hexyl).

The term “heteroalkyl” refers to a linear or branched saturated monovalent hydrocarbon radical that contains one or more heteroatoms on its main chain, each independently selected from O, S, and N. The heteroalkyl is optionally substituted with one or more substituents Q as described herein. For example, C_1-6heteroalkyl refers to a linear saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the heteroalkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (C_1-20), 1 to 15 (C_1-15), i to 10 (C_1-10), or 1 to 6 (C_1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20 (C₃-20), 3 to 15 (C_3-15), 3 to 10 (C_3-10), or 3 to 6 (C_3-6) carbon atoms. As used herein, linear C_1-6and branched C_3-6heteroalkyl groups are also referred as “lower heteroalkyl.” Examples of heteroalkyl groups include, but are not limited to, —OCH₃, —OCH₂CH₃, —CH₂OCH₃, —NHCH₃, —ONHCH₃, —NHOCH₃, —SCH₃, —CH₂NHCH₂CH₃, and —NHCH₂CH₂CH₃. Examples of substituted heteroalkyl groups include, but are not limited to, —CH₂NHC(O)CH₃and —NHC(O)CH₂CH₃.

The term “alkenyl” refers to a linear or branched monovalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon double bond(s). The alkenyl is optionally substituted with one or more substituents Q as described herein. The term “alkenyl” embraces radicals having a “cis” or “trans” configuration or a mixture thereof, or alternatively, a “Z” or “E” configuration or a mixture thereof, as appreciated by those of ordinary skill in the art. For example, C_2-6alkenyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkenyl is a linear monovalent hydrocarbon radical of 2 to 20 (C_2-20), 2 to 15 (C_2-15), 2 to 10 (C_2-10), or 2 to 6 (C_2-6) carbon atoms, or a branched monovalent hydrocarbon radical of 3 to 20 (C_3-20), 3 to 15 (C_3-15), 3 to 10 (C_3-10), or 3 to 6 (C_3-6) carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, propenyl (including all isomeric forms, e.g., propen-1-yl, propen-2-yl, and allyl), and butenyl (including all isomeric forms, e.g., buten-1-yl, buten-2-yl, buten-3-yl, and 2-buten-1-yl).

The term “alkynyl” refers to a linear or branched monovalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon triple bond(s). An alkynyl group does not contain a carbon-carbon double bond. The alkynyl is optionally substituted with one or more substituents Q as described herein. For example, C_2-6alkynyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated monovalent hydrocarbon radical of 4 to 6 carbon atoms. In certain embodiments, the alkynyl is a linear monovalent hydrocarbon radical of 2 to 20 (C_2-20), 2 to 15 (C_2-15), 2 to 10 (C_2-10), or 2 to 6 (C_2-6) carbon atoms, or a branched monovalent hydrocarbon radical of 4 to 20 (C_4-20), 4 to 15 (C_4-15), 4 to 10 (C_4-10), or 4 to 6 (C_4-6) carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (—C≡CH), propynyl (including all isomeric forms, e.g., 1-propynyl (—C≡CCH3) and propargyl (—CH₂C≡CH)), butynyl (including all isomeric forms, e.g., 1-butyn-1-yl and 2-butyn-1-yl), pentynyl (including all isomeric forms, e.g., 1-pentyn-1-yl and 1-methyl-2-butyn-1-yl), and hexynyl (including all isomeric forms, e.g., 1-hexyn-1-yl and 2-hexyn-1-yl).

The term “cycloalkyl” refers to a cyclic monovalent hydrocarbon radical, which is optionally substituted with one or more substituents Q as described herein. In one embodiment, the cycloalkyl is a saturated or unsaturated but non-aromatic, and/or bridged or non-bridged, and/or fused and/or spiro bicyclic group. In certain embodiments, the cycloalkyl has from 3 to 20 (C_3-20), from 3 to 15 (C_3-15), from 3 to 10 (C_3-10), or from 3 to 7 (C_3-7) carbon atoms. In one embodiment, the cycloalkyl is monocyclic. In another embodiment, the cycloalkyl is bicyclic. In yet another embodiment, the cycloalkyl is tricyclic. In still another embodiment, the cycloalkyl is polycyclic. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, decalinyl, and adamantyl.

The term “aryl” refers to a monovalent monocyclic aromatic hydrocarbon radical and/or monovalent polycyclic aromatic hydrocarbon radical that contain at least one aromatic carbon ring. In certain embodiments, the aryl has from 6 to 20 (C_6-20), from 6 to 15 (C_6-15), or from 6 to 10 (C_6-10) ring carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, fluorenyl, azulenyl, anthryl, phenanthryl, pyrenyl, biphenyl, and terphenyl. The aryl also refers to bicyclic or tricyclic carbon rings, where one of the rings is aromatic and the others of which may be saturated, partially unsaturated, or aromatic, for example, dihydronaphthyl, indenyl, indanyl, or tetrahydronaphthyl (tetralinyl). In one embodiment, the aryl is monocyclic. In another embodiment, the aryl is bicyclic. In yet another embodiment, the aryl is tricyclic. In still another embodiment, the aryl is polycyclic. In certain embodiments, the aryl is optionally substituted with one or more substituents Q as described herein.

The term “aralkyl” or “arylalkyl” refers to a monovalent alkyl group substituted with one or more aryl groups. In certain embodiments, the aralkyl has from 7 to 30 (C_7-30), from 7 to 20 (C_7-20), or from 7 to 16 (C_7-16) carbon atoms. Examples of aralkyl groups include, but are not limited to, benzyl, phenylethyl (including all isomeric forms, e.g., 1-phenylethyl and 2-phenylethyl), and phenylpropyl (including all isomeric forms, e.g., 1-phenylpropyl, 2-phenylpropyl, and 3-phenylpropyl). In certain embodiments, the aralkyl is optionally substituted with one or more substituents Q as described herein.

The term “heteroaryl” refers to a monovalent monocyclic aromatic group or monovalent polycyclic aromatic group that contain at least one aromatic ring, wherein at least one aromatic ring contains one or more heteroatoms, each independently selected from O, S, and N, in the ring. For a heteroaryl group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heteroaryl group is not bonded to the rest of a molecule through its nonaromatic heterocyclic ring. Each ring of a heteroaryl group can contain one or two O atoms, one or two S atoms, and/or one to four N atoms; provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl has from 5 to 20, from 5 to 15, or from 5 to 10 ring atoms. In one embodiment, the heteroaryl is monocyclic. Examples of monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, and triazolyl. In another embodiment, the heteroaryl is bicyclic. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzoisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furopyrindyl (including all isomeric forms, e.g., furo[2,3-b]pyridinyl, furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, furo[3,4-b]pyridinyl, and furo[3,4-c]pyridinyl), imidazopyridinyl (including all isomeric forms, e.g., imidazo[1,2-a]pyridinyl, imidazo[4,5-b]pyridinyl, and imidazo[4,5-c]pyridinyl), imidazothiazolyl (including all isomeric forms, e.g., imidazo[2,1-b]thiazolyl and imidazo[4,5-d]thiazolyl), indazolyl, indolizinyl, indolyl, isobenzofuranyl, isobenzothienyl (i.e., benzo[c]thienyl), isoindolyl, isoquinolinyl, naphthyridinyl (including all isomeric forms, e.g., 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, and 1,8-naphthyridinyl), oxazolopyridinyl (including all isomeric forms, e.g., oxazolo[4,5-b]pyridinyl, oxazolo[4,5-c]pyridinyl, oxazolo[5,4-b]pyridinyl, and oxazolo[5,4-c]pyridinyl), phthalazinyl, pteridinyl, purinyl, pyrrolopyridyl (including all isomeric forms, e.g., pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-b]pyridinyl, and pyrrolo[3,2-c]pyridinyl), quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl (including all isomeric forms, e.g., [1,2,5]thiadiazolo[3,4-d]pyrimidinyl and [1,2,3]thiadiazolo[4,5-d]pyrimidinyl), and thienopyridyl (including all isomeric forms, e.g., thieno[2,3-b]pyridinyl, thieno[2,3-c]pyridinyl, thieno[3,2-b]pyridinyl, and thieno[3,2-c]pyridinyl). In yet another embodiment, the heteroaryl is tricyclic. Examples of tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinyl (including all isomeric forms, e.g., 1,5-phenanthrolinyl, 1,6-phenanthrolinyl, 1,7-phenanthrolinyl, 1,9-phenanthrolinyl, and 2,10-phenanthrolinyl), phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, the heteroaryl is optionally substituted with one or more substituents Q as described herein.

The term “heterocyclyl” or “heterocyclic” refers to a monovalent monocyclic non-aromatic ring system or monovalent polycyclic ring system that contains at least one non-aromatic ring, wherein one or more of the non-aromatic ring atoms are heteroatoms, each independently selected from O, S, and N; and the remaining ring atoms are carbon atoms. For a heterocyclyl group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heterocyclyl group is not bonded to the rest of a molecule through the heteroaromatic ring. In certain embodiments, the heterocyclyl or heterocyclic group has from 3 to 20, from 3 to 15, from 3 to 10, from 3 to 8, from 4 to 7, or from 5 to 6 ring atoms. In certain embodiments, the heterocyclyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be fused or bridged, and in which nitrogen or sulfur atoms may be optionally oxidized, nitrogen atoms may be optionally quaternized, and some rings may be partially or fully saturated, or aromatic. The heterocyclyl may be attached to the main structure at any heteroatom or carbon atom which results in the creation of a stable compound. Examples of heterocyclyls and heterocyclic groups include, but are not limited to, azepinyl, benzodioxanyl, benzodioxolyl, benzofuranonyl, chromanyl, decahydroisoquinolinyl, dihydrobenzofuranyl, dihydrobenzisothiazolyl, dihydrobenzisoxazinyl (including all isomeric forms, e.g., 1,4-dihydrobenzo[d][1,3]oxazinyl, 3,4-dihydrobenzo[c][1,2]-oxazinyl, and 3,4-dihydrobenzo[d][1,2]oxazinyl), dihydrobenzothienyl, dihydroisobenzofuranyl, dihydrobenzo[c]thienyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, thiochromanyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain embodiments, the heterocyclyl is optionally substituted with one or more substituents Q as described herein.

The term “halogen”, “halide,” or “halo” refers to fluoro, chloro, bromo, and/or iodo.

The term “optionally substituted” is intended to mean that a group or substituent, such as an alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heterocyclyl group, may be substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, each of which is independently selected from, e.g., (a) deuterium (—D), cyano (—CN), halo, imino (═NH), nitro (—NO₂), and oxo (═O); (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; and (c) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —C(O)SR^a, —C(NR^a)NR^bR^c, —C(S)R^a, —C(S)OR^a, —C(S)NR^bR^c, —OR^a, —OC(O)R^a, —OC(O)OR^a, —OC(O)NR^bR^c, —OC(O)SR^a, —OC(NR^a)NR^bR^c, —OC(S)R^a, —OC(S)OR^a, —OC(S)NR^bR^c, —OP(O)(OR^b)OR^c, —OS(O)R^a, —OS(O)₂R^a, —OS(O)NR^bR^c, —OS(O)₂NR^bR^c, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aC(O)NR^bR^c, —NR^aC(O)SR^d, —NR^aC(NR^d)NR^bR^c, —NR^aC(S)R^d, —NR^aC(S)OR^d, —NR^aC(S)NR^bR^c, —NR^aS(O)R^d, —NR^aS(O)₂R^d, —NR^aS(O)NR^bR^c, —NR^aS(O)₂NR^bR^c, —SR^a, —S(O)R^a, —S(O)₂R^a, —S(O)NR^bR^c, and —S(O)₂NR^bR^c, wherein each R^a, R^b, R^c, and R^dis independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_1-6C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; or (iii) R^band R^ctogether with the N atom to which they are attached form heterocyclyl optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a. As used herein, all groups that can be substituted are “optionally substituted.”

In one embodiment, each Q^ais independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, and heterocyclyl; and (c) —C(O)R^e, —C(O)OR^e, —C(O)NR^fR^g, —C(O)SR^e, —C(NR^e)NR^fR^g, —C(S)R^e, —C(S)OR^e, —C(S)NR^fR^g, —OR^e, —OC(O)R^e, —OC(O)OR^e, —OC(O)NR^fR^g, —OC(O)SR^e, —OC(NR^e)NR^fR^g, —OC(S)R^e, —OC(S)OR^e, —OC(S)NR^fR^g, —OP(O)(OR^f)OR^g, —OS(O)R^e, —OS(O)₂R^e, —OS(O)NR^fR^g, —OS(O)₂NR^fR^g, —NR^fR^g, —NR^eC(O)R^h, —NR^eC(O)OR^f, —NR^eC(O)NR^fR^g, —NR^eC(O)SR^f, —NR^eC(NR^h)NR^fR^g, —NR^eC(S)R^h, —NR^eC(S)OR^f, —NR^eC(S)NR^fR^g, —NR^eS(O)R^h, —NR^eS(O)₂R^h, —NR^eS(O)NR^fR^g, —NR^eS(O)₂NR^fR^g, —SR^e, —S(O)R^e, —S(O)₂R^e, —S(O)NR^fR^g, and —S(O)₂NR^fR^g; wherein each R^e, R^f, R^g, and R^his independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) R^fand R^gtogether with the N atom to which they are attached form heterocyclyl.

In certain embodiments, “optically active” and “enantiomerically active” refer to a collection of molecules, which has an enantiomeric excess of no less than about 80%, no less than about 90%, no less than about 91%, no less than about 92%, no less than about 93%, no less than about 94%, no less than about 95%, no less than about 96%, no less than about 97%, no less than about 98%, no less than about 99%, no less than about 99.5%, or no less than about 99.8%. In certain embodiments, an optically active compound comprises about 95% or more of one enantiomer and about 5% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question. In certain embodiments, an optically active compound comprises about 98% or more of one enantiomer and about 2% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question. In certain embodiments, an optically active compound comprises about 99% or more of one enantiomer and about 1% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question.

In describing an optically active compound, the prefixes R and S are used to denote the absolute configuration of the compound about its chiral center(s). The (+) and (−) are used to denote the optical rotation of the compound, that is, the direction in which a plane of polarized light is rotated by the optically active compound. The (−) prefix indicates that the compound is levorotatory, that is, the compound rotates the plane of polarized light to the left or counterclockwise. The (+) prefix indicates that the compound is dextrorotatory, that is, the compound rotates the plane of polarized light to the right or clockwise. However, the sign of optical rotation, (+) and (−), is not related to the absolute configuration of the compound, R and S.

The term “isotopically enriched” refers to a compound that contains an unnatural proportion of an isotope at one or more of the atoms that constitute such a compound. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen (¹H), deuterium (²H), tritium (³H), carbon-11 (¹¹C), carbon-12 (¹²C), carbon-13 (¹³C), carbon-14 (¹⁴C), nitrogen-13 (¹³N), nitrogen-14 (¹⁴N), nitrogen-15 (¹⁵N), oxygen-14 (¹⁴O), oxygen-15 (¹⁵O), oxygen-16 (¹⁶O), oxygen-17 (¹⁷O), oxygen-18 (¹⁸O), fluorine-17 (¹⁷F), fluorine-18 (¹⁸F), phosphorus-31 (³¹P), phosphorus-32 (³²P), phosphorus-33 (³³P), sulfur-32 (³²S), sulfur-33 (³³S), sulfur-34 (³⁴S), sulfur-35 (³⁵S), sulfur-36 (³⁶S), chlorine-35 (³⁵Cl), chlorine-36 (³⁶Cl), chlorine-37 (³⁷Cl), bromine-79 (⁷⁹Br), bromine-81 (⁸¹Br), iodine-123 (¹²³I), iodine-125 (¹²⁵I), iodine-127 (¹²⁷1), iodine-129 (¹²⁹I), and iodine-131 (¹³¹I). In certain embodiments, an isotopically enriched compound is in a stable form, that is, non-radioactive. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen (¹H), deuterium (²H), carbon-12 (¹²C), carbon-13 (¹³C), nitrogen-14 (¹⁴N), nitrogen-15 (¹⁵N), oxygen-16 (¹⁶O), oxygen-17 (¹⁷O), oxygen-18 (¹⁸O), fluorine-17 (¹⁷F), phosphorus-31 (³¹P), sulfur-32 (³²S), sulfur-33 (³³S), sulfur-34 (³⁴S), sulfur-36 (³⁶S), chlorine-35 (³⁵Cl), chlorine-37 (³⁷Cl), bromine-79 (⁷⁹Br), bromine-81 (⁸¹Br), and iodine-127 (¹²⁷I). In certain embodiments, an isotopically enriched compound is in an unstable form, that is, radioactive. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, tritium (H), carbon-11 (¹¹C), carbon-14 (¹⁴C), nitrogen-13 (¹³N), oxygen-14 (¹⁴O), oxygen-15 (¹⁵O), fluorine-18 (¹⁸F), phosphorus-32 (³²P), phosphorus-33 (³³P), sulfur-35 (³⁵S), chlorine-36 (³⁶Cl), iodine-123 (¹²³I), iodine-125 (¹²⁵I), iodine-129 (¹²⁹I), and iodine-131 (¹³¹I). It will be understood that, in a compound as provided herein, any hydrogen can be ²H, as example, or any carbon can be ¹³C, as example, or any nitrogen can be ¹⁵N, as example, or any oxygen can be ¹⁸O, as example, where feasible according to the judgment of one of ordinary skill in the art.

The term “isotopic enrichment” refers to the percentage of incorporation of a less prevalent isotope (e.g., D for deuterium or hydrogen-2) of an element at a given position in a molecule in the place of a more prevalent isotope (e.g., ¹H for protium or hydrogen-1) of the element. As used herein, when an atom at a particular position in a molecule is designated as a particular less prevalent isotope, it is understood that the abundance of that isotope at that position is substantially greater than its natural abundance.

The term “isotopic enrichment factor” refers the ratio between the isotopic abundance in an isotopically enriched compound and the natural abundance of a specific isotope.

The term “hydrogen” or the symbol “H” refers to the composition of naturally occurring hydrogen isotopes, which include protium (¹H), deuterium (²H or D), and tritium (³H), in their natural abundances. Protium is the most common hydrogen isotope having a natural abundance of more than 99.98%. Deuterium is a less prevalent hydrogen isotope having a natural abundance of about 0.0156%.

The term “deuterium enrichment” refers to the percentage of incorporation of deuterium at a given position in a molecule in the place of hydrogen. For example, deuterium enrichment of 1% at a given position means that 1% of molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156% on average, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156% on average. As used herein, when a particular position in an isotopically enriched compound is designated as having deuterium, it is understood that the abundance of deuterium at that position in the compound is substantially greater than its natural abundance (0.0156%).

The term “carbon” or the symbol “C” refers to the composition of naturally occurring carbon isotopes, which include carbon-12 (¹²C) and carbon-13 (¹³C) in their natural abundances. Carbon-12 is the most common carbon isotope having a natural abundance of more than 98.89%. Carbon-13 is a less prevalent carbon isotope having a natural abundance of about 1.11%.

The term “carbon-13 enrichment” or “¹³C enrichment” refers to the percentage of incorporation of carbon-13 at a given position in a molecule in the place of carbon. For example, carbon-13 enrichment of 10% at a given position means that 10% of molecules in a given sample contain carbon-13 at the specified position. Because the naturally occurring distribution of carbon-13 is about 1.11% on average, carbon-13 enrichment at any position in a compound synthesized using non-enriched starting materials is about 1.11% on average. As used herein, when a particular position in an isotopically enriched compound is designated as having carbon-13, it is understood that the abundance of carbon-13 at that position in the compound is substantially greater than its natural abundance (1.11%).

The terms “substantially pure” and “substantially homogeneous” mean, when referred to a substance, sufficiently homogeneous to appear free of readily detectable impurities as determined by a standard analytical method used by one of ordinary skill in the art, including, but not limited to, thin layer chromatography (TLC), gel electrophoresis, high performance liquid chromatography (HPLC), gas chromatography (GC), nuclear magnetic resonance (NMR), and mass spectrometry (MS); or sufficiently pure such that further purification would not detectably alter the physical, chemical, biological, and/or pharmacological properties, such as enzymatic and biological activities, of the substance. In certain embodiments, “substantially pure” or “substantially homogeneous” refers to a collection of molecules, wherein at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% by weight of the molecules are a single compound, including a single enantiomer, a racemic mixture, or a mixture of enantiomers, as determined by standard analytical methods. As used herein, when an atom at a particular position in an isotopically enriched molecule is designated as a particular less prevalent isotope, a molecule that contains other than the designated isotope at the specified position is an impurity with respect to the isotopically enriched compound. Thus, for a deuterated compound that has an atom at a particular position designated as deuterium, a compound that contains a protium at the same position is an impurity.

The term “solvate” refers to a complex or aggregate formed by one or more molecules of a solute, e.g., a compound provided herein, and one or more molecules of a solvent, which are present in a stoichiometric or non-stoichiometric amount. Suitable solvents include, but are not limited to, water, methanol, ethanol, n-propanol, isopropanol, and acetic acid. In certain embodiments, the solvent is pharmaceutically acceptable. In one embodiment, the complex or aggregate is in a crystalline form. In another embodiment, the complex or aggregate is in a noncrystalline form. Where the solvent is water, the solvate is a hydrate. Examples of hydrates include, but are not limited to, a hemihydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate.

For a divalent group described herein, no orientation is implied by the direction in which the divalent group is presented. For example, unless a particular orientation is specified, the formula —C(O)NH— represents both —C(O)NH— and —NHC(O)—.

The phrase “an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof” has the same meaning as the phrase “(i) an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant of the compound referenced therein; (ii) a pharmaceutically acceptable salt, solvate, hydrate, or prodrug of the compound referenced therein; or (iii) a pharmaceutically acceptable salt, solvate, hydrate, or prodrug of an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant of the compound referenced therein.”

Compounds

In one embodiment, provided herein is a compound of Formula (I):

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- R¹is hydrogen, deuterium, or C_1-6alkyl;
- R²is hydrogen or C_1-6alkyl;
- R³and R⁴are:
- (i) R³is halo; and
  - R⁴is

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- - or
- (ii) R³is hydrogen, deuterium, or halo; and
  - R⁴is

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- each R⁵is independently (i) deuterium, cyano, halo, or nitro; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) —C(O)R^1a, —C(O)OR^1a, —C(O)NR^1bR^1c, —C(O)SR^1a—C(NR^1a)NR^1bR^1c, —C(S)R^1a, —C(S)OR^1a, —C(S)NR^1bR^1c, —OR^1a, —OC(O)R^1a, —OC(O)OR^1a, —OC(O)NR^1bR^1c, —OC(O)SR^1a, —OC(NR^1a)NR^1bR^1c, —OC(S)R^1a, —OC(S)OR^1a, —OC(S)NR^1bR^1c, —OS(O)R^1a, —OS(O)₂R^1a, —OS(O)NR^1bR^1c, —OS(O)₂NR^1bR^1c, —NR^1bR^1c, —NR^1aC(O)R^1d, —NR^1aC(O)OR^1d, —NR^1aC(O)NR^1bR^1c, —NR^1aC(O)SR^1d, —NR^1aC(NR^1d)NR^1bR^1c, —NR^1aC(S)R^1d, —NR^1aC(S)OR^1d, —NR^1aC(S)NR^1bR^1c, —NR^1aS(O)R^1d, —NR^1aS(O)₂R^1d, —NR^1aS(O)NR^1bR^1c, —NR^1aS(O)₂NR^1bR^1c, —SR^1a, —S(O)R^1a, —S(O)₂R^1a, —S(O)NR^1bR^1c, or —S(O)₂NR^1bR^1c;
- each R⁶is independently C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl;
- each R^1a, R^1b, R^1c, and R^1dis independently hydrogen, deuterium, C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl;
- each A is independently CR^4aor N; wherein R^4ais hydrogen, deuterium, halo, C_1-6alkyl, or C_1-6heteroalkyl;
- each X is independently —(CH₂)_n—, —C(O)—, —S(O)—, or —S(O₂)—; wherein n is an integer of 1, 2, 3, 4, or 5;
- each a, b, c, d, e, and f is independently an integer of 0, 1, 2, or 3;
- m is an integer of 0, 1, 2, or 3;
- wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, and heterocyclyl is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; and (c) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —C(O)SR^a, —C(NR^a)NR^bR^c, —C(S)R^a, —C(S)OR^a, —C(S)NR^bR^c, —OR^a, —OC(O)R^a, —OC(O)OR^a, —OC(O)NR^bR^c, —OC(O)SR^a, —OC(NR^a)NR^bR^c, —OC(S)R^a, —OC(S)OR^a, —OC(S)NR^bR^c, —OP(O)(OR^b)OR^c, —OS(O)R^a, —OS(O)₂R^a, —OS(O)NR^bR^c, —OS(O)₂NR^bR^c, —NR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aC(O)NR^bR^c, —NR^aC(O)SR^d, —NR^aC(NR^d)NR^bR^c, —NR^aC(S)R^d, —NR^aC(S)OR^d, —NR^aC(S)NR^bR^c, —NR^aS(O)R^d, —NR^aS(O)₂R^d, —NR^aS(O)NR^bR^c, —NR^aS(O)₂NR^bR^c, —SR^a, —S(O)R^a, —S(O)₂R^a, —S(O)NR^bR^c, and —S(O)₂NR^bR^c, wherein each R^a, R^b, R^c, and R^dis independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; or (iii) R^band R^ctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q^a; wherein each Q^ais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, and heterocyclyl; and (c) —C(O)R^e, —C(O)OR^e, —C(O)NR^fR^g, —C(O)SR^e, —C(NR^c)NR^fR^g, —C(S)R^e, —C(S)OR^e, —C(S)NR^fR^g, —OR^e, —OC(O)R^e, —OC(O)OR^e, —OC(O)NR^fR^g, —OC(O)SR^e, —OC(NR^e)NR^fR^g, —OC(S)R^e, —OC(S)OR^e, —OC(S)NR^fR^g, —OP(O)(OR^f)OR^g, —OS(O)R^e, —OS(O)₂R^e, —OS(O)NR^fR^g, —OS(O)₂NR^fR^g, —NR^fR^g, —NR^eC(O)R^h, —NR^eC(O)OR^f, —NR^eC(O)NR^fR^g, —NR^eC(O)SR^f, —NR^eC(NR^h)NR^fR^g, —NR^eC(S)R^h, —NR^eC(S)OR^f, —NR^eC(S)NR^fR^g, —NR^eS(O)R^h, —NR^eS(O)₂R^h, —NR^eS(O)NR^fR^g, —NR^eS(O)₂NR^fR^g, —SR^e, —S(O)R^e, —S(O)₂R^e, —S(O)NR^fR^g, and —S(O)₂NR^fR^g; wherein each R^e, R^f, R^g, and R^his independently (i) hydrogen or deuterium; (ii) C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) R^fand R^gtogether with the N atom to which they are attached form heterocyclyl.

In another embodiment, provided herein is a compound of Formula (II):

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In yet another embodiment, provided herein is a compound of Formula (III):

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In certain embodiments, in Formula (I), (II), or (III), a and b are each independently an integer of 0, 1, or 2. In certain embodiments, in Formula (I), (II), or (III), a and b are each independently an integer of 0 or 1. In certain embodiments, in Formula (I), (II), or (III), a and b are each an integer of 1.

In yet another embodiment, provided herein is a compound of Formula (IV):

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In certain embodiments, in any one of Formulae (I) to (IV), A is CR^4a, wherein R^4ais as defined herein. In certain embodiments, in any one of Formulae (I) to (IV), A is CH. In certain embodiments, in any one of Formulae (I) to (IV), A is N.

In yet another embodiment, provided herein is a compound of Formula (V):

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In yet another embodiment, provided herein is a compound of Formula (VI):

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In yet another embodiment, provided herein is a compound of Formula (VII):

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In certain embodiments, in Formula (VII), a and b are each independently an integer of 0, 1, or 2. In certain embodiments, in Formula (VII), a and b are each independently an integer of 0 or 1. In certain embodiments, in Formula (VII), a and b are each an integer of 1.

In yet another embodiment, provided herein is a compound of Formula (VIII):

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In certain embodiments, in Formula (VIII), A is CR^4a, wherein R^4ais as defined herein. In certain embodiments, in Formula (VIII), A is CH. In certain embodiments, in Formula (VIII), A is N.

In yet another embodiment, provided herein is a compound of Formula (IX):

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In yet another embodiment, provided herein is a compound of Formula (X):

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In yet another embodiment, provided herein is a compound of Formula (XI):

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In yet another embodiment, provided herein is a compound of Formula (XII):

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In certain embodiments, in Formula (I), (XI), or (XII), c, d, e, and f are each independently an integer of 0, 1, or 2. In certain embodiments, in Formula (I), (XI), or (XII), c, d, e, and f are each independently an integer of 0 or 1. In certain embodiments, in Formula (I), (XI), or (XII), c and d are each an integer of 1; and e and f are each an integer of 0.

In yet another embodiment, provided herein is a compound of Formula (XIII):

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In certain embodiments, in any one of Formulae (XI) to (XIII), A is CR^4a, wherein R^4ais as defined herein. In certain embodiments, in any one of Formulae (XI) to (XIII), A is CH. In certain embodiments, in any one of Formulae (XI) to (XIII), A is N.

In yet another embodiment, provided herein is a compound of Formula (XIV):

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In yet another embodiment, provided herein is a compound of Formula (XV):

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In yet another embodiment, provided herein is a compound of Formula (XVI):

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In certain embodiments, in Formula (XVI), c, d, e, and f are each independently an integer of 0, 1, or 2. In certain embodiments, in Formula (XVI), c, d, e, and f are each independently an integer of 0 or 1. In certain embodiments, in Formula (XVI), c and d are each an integer of 1; and e and f are each an integer of 0.

In yet another embodiment, provided herein is a compound of Formula (XVII):

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In certain embodiments, in Formula (XVII), A is CR^4a, wherein R^4ais as defined herein. In certain embodiments, in Formula (XVII), A is CH. In certain embodiments, in Formula (XVI), A is N.

In yet another embodiment, provided herein is a compound of Formula (XVIII):

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In still another embodiment, provided herein is a compound of Formula (XIX):

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In certain embodiments, in any one of Formulae (I) to (XIX), R¹is hydrogen. In certain embodiments, in any one of Formulae (I) to (XIX), R¹is deuterium. In certain embodiments, in any one of Formulae (I) to (XIX), R¹is C_1-6alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R¹is methyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R²is hydrogen. In certain embodiments, in any one of Formulae (I) to (XIX), R²is C_1-6alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R²is methyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R²is C_1-6alkyl substituted with —C(O)R^aor —OP(O)(OR^b)OR^c, wherein R^a, R^b, and R^aare each as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R²is methyl substituted with —C(O)R^aor —OP(O)(OR^b)OR^c, wherein R^a, R^b, and R^aare each as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R²is valyloxymethyl or di-tert-butoxyphosphoryloxymethyl. In certain embodiments, in any one of Formulae (I) to (XIX), R²is D-valyloxymethyl or L-valyloxymethyl.

In certain embodiments, in any one of Formulae (I) and (XI) to (XIX), R³is hydrogen. In certain embodiments, in any one of Formulae (I) and (XI) to (XIX), R³is deuterium. In certain embodiments, in any one of Formulae (I) to (XIX), R³is halo. In certain embodiments, in any one of Formulae (I) to (XIX), R³is fluoro, chloro, or bromo. In certain embodiments, in any one of Formulae (I) to (XIX), R³is fluoro. In certain embodiments, in any one of Formulae (I) to (XIX), R³is chloro. In certain embodiments, in any one of Formulae (I) to (XIX), R³is bromo.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_1-6alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_1-6alkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —N^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_1-6alkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) halo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —OR^a, —NR^bR^c, or —NR^aC(O)OR^d; wherein each R^a, R^b, R^c, and R^dis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_1-6alkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_1-6alkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently fluoro, chloro, methyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 5-methylfuran-2-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-3-yl, 2-methoxypyridin-3-yl, quinoline-6-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonyl-piperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, hydroxyl, 3-methylphenoxy, benzoxy, methylamino, or tert-butoxycarbonylamino.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is methyl, ethyl, propyl, or butyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is methyl, ethyl, propyl, or butyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently fluoro, chloro, methyl, trifluoromethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 5-methylfuran-2-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-3-yl, 2-methoxypyridin-3-yl, quinoline-6-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, hydroxyl, 3-methylphenoxy, benzoxy, methylamino, or tert-butoxycarbonylamino.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is ethyl, propyl, isopropyl, isobutyl, trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 3-chloropropyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, (3-methylphenoxy)methyl, benzyl, 2-phenylethyl, 3-phenylpropyl, 2-(3-bromophenyl)ethyl, 2-methyl-2-phenylpropyl, 2-(3-trifluoro-methylphenyl)ethyl, 2-(2-methoxyphenyl)ethyl, 2-benzoxyethyl, 2-(5-methylfuran-2-yl)ethyl, pyrazol-1-ylmethyl, pyrrol-2-ylmethyl, 2-(pyrrol-2-yl)ethyl, 1,2,3-triazol-1-ylmethyl, pyrimidin-2-ylmethyl, pyrimidin-5-ylmethyl, 2-methoxypyridin-3-ylmethyl, 2-(pyridin-2-yl)ethyl, 2-(pyridin-3-yl)ethyl, 2-(quinolin-6-yl)ethyl, pyrrolidin-1-ylmethyl, tetrahydropyran-4-ylmethyl, piperidin-1-ylmethyl, 1-benzoxycarbonylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)-piperidin-4-ylmethyl, 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)prop-2-yl, 4-(tert-butoxy-carbonyl)piperazin-1-ylmethyl, morpholinomethyl, 3-hydroxy-2-methylprop-2-yl, benzoxy-methyl, 2-benzoxyethyl, methylaminomethyl, or (tert-butoxycarbonyl)aminomethyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_1-6heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, or 3-chloropropyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_2-6alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_2-6alkynyl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_3-10cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_3-10monocyclic cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_4-10bicyclic cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_5-10bridged cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_4-10fused cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_5-10spiro cycloalkyl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_3-10cycloalkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_3-10cycloalkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) halo; (ii) C_1-6alkyl, optionally substituted with one or more substituents Q^a; or (iii) —OR^a, —R^bR^c, or —NR^aC(O)OR^d, wherein each R^a, R^b, R^c, and R^dis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_3-10cycloalkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)-piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxy-carbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_3-10cycloalkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently fluoro, methyl, (tert-butoxycarbonylamino)methyl, hydroxyl, amino, or tert-butoxycarbonylamino.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[2.2.2]octanyl, or adamantanyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methyl-phenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxy-pyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylamino-carbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxy-carbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[2.2.2]octanyl, or adamantanyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently fluoro, methyl, (tert-butoxy-carbonylamino)methyl, hydroxyl, amino, or tert-butoxycarbonylamino.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is cyclopropyl, cyclobutyl, 3,3-dimethylcyclobut-1-yl, cyclopentyl, cyclohexyl, adamantan-1-yl, 1-fluorocyclopropyl, 4,4-difluorocyclohexyl, 3,3-dimethylcyclobutyl, 4-hydroxybicyclo[2.2.2]octan-1-yl, 1-aminocyclobutyl, 4-(tert-butoxycarbonylamino)cyclohexyl, or 4-(tert-butoxycarbonylamino-methyl)cyclohexyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_6-14aryl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_6-14aryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_6-14aryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano or halo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_6-14aryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_6-14aryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, methyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, 1,2,4-triazol-1-yl, pyridin-4-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclopentoxy, cyclohexylmethoxy, phenoxy, 4-cyanophenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano or halo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, methyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, 1,2,4-triazol-1-yl, pyridin-4-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclopentoxy, cyclohexylmethoxy, phenoxy, 4-cyanophenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, substituted with one substituent Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoro-methylphenyl, 3-hydroxymethylphenyl, 4-hydroxymethylphenyl, 4-((dimethylamino)methyl)-phenyl, 2-ethynylphenyl, 3-ethynylphenyl, 4-ethynylphenyl, 2-cyclopropylphenyl, 4-cyclopropylphenyl, 4-phenylphenyl, 4-benzylphenyl, 3-(imidazol-1-yl)-phenyl, 4-(imidazol-1-yl)-phenyl, 4-(oxazol-5-yl)phenyl, 4-(pyrazol-1-yl)phenyl, 2-(1,2,4-triazol-1-yl)-phenyl, 3-(1,2,4-triazol-1-yl)phenyl, 4-(1,2,4-triazol-1-yl)phenyl, 3-(pyridin-4-yl)phenyl, 3-(pyrrolidin-1-yl)phenyl, 4-(pyrrolidin-1-yl)phenyl, 2-(morpholino)phenyl, 3-(morpholino)phenyl, 4-(morpholino)phenyl, 3-aminocarbonylphenyl, 4-aminocarbonylphenyl, 4-(methylamino-carbonyl)phenyl, 2-(dimethylaminocarbonyl)phenyl, 4-(isopropylaminocarbonyl)phenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl, 4-cyclopentoxyphenyl, 3-(cyclohexylmethoxy)phenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, 3-(4-cyanophenoxy)phenyl, 4-(4-cyanophenoxy)phenyl, 4-(4-trifluoromethylphenoxy)phenyl, 4-(4-cyano-2-fluorophenoxy)-phenyl, 3-benzoxyphenyl, 4-benzoxyphenyl, 3-(4-cyanobenzoxy)phenyl, 4-(4-cyanobenzoxy)-phenyl, 2-(pyridin-2-yloxy)phenyl, 4-(pyridin-2-yloxy)phenyl, 4-(pyridin-3-yloxy)phenyl, 3-morpholinophenyl, 4-morpholinophenyl, 2-aminophenyl, 4-aminophenyl, 2-methylaminophenyl, 4-ethylaminophenyl, 2-(dimethylamino)phenyl, 3-(dimethylamino)phenyl, 4-(dimethylamino)-phenyl, 4-(2-hydroxyethyl)(methyl)amino)phenyl, 3-acetamidophenyl, 4-acetamidophenyl, 4-benzoxycarbonylaminophenyl, 4-methylsulfonylaminophenyl, 2-methylsulfonylaminophenyl, 3-methylsulfonylaminophenyl, or 4-(ethylsulfonyl)phenyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, substituted with two substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 2-amino-3-chlorophenyl, 2-amino-4-chlorophenyl, 2-amino-6-chlorophenyl, 2-amino-5-fluorophenyl, 2-benzoxy-4-methylphenyl, 4-benzoxy-2-methylphenyl, 2-bromo-4-(4-cyanophenoxy)phenyl, 2-bromo-5-(4-cyanophenoxy)phenyl, 3-bromo-4-(4-methylpiperazin-1-yl)phenyl, 3-bromo-4-morpholinophenyl, 2-chloro-4-cyanophenyl, 3-chloro-4-cyanophenyl, 3-chloro-5-cyanophenyl, 4-chloro-3-cyanophenyl, 2-chloro-6-methylphenyl, 3-chloro-4-methyl-phenyl, 2-chloro-4-morpholinophenyl, 3-chloro-4-morpholinophenyl, 2-chloro-4-trifluoro-methylphenyl, 2-chloro-5-trifluoromethylphenyl, 3-chloro-4-trifluoromethylphenyl, 4-chloro-2-trifluoromethylphenyl, 5-chloro-2-trifluoromethylphenyl, 2-cyano-4-fluorophenyl, 2-cyano-5-fluorophenyl, 3-cyano-4-fluorophenyl, 3-cyano-5-fluorophenyl, 4-cyano-3-fluorophenyl, 4-cyano-2-fluorophenyl, 5-cyano-2-fluorophenyl, 3-cyano-4-(4-methylimidazol-1-yl)phenyl, 3-cyano-4-hydroxyphenyl, 4-cyano-2-hydroxyphenyl, 2-cyano-4-methoxyphenyl, 4-cyano-2-methoxyphenyl, 4-cyano-3-methoxyphenyl, 4-cyano-3-methoxyphenyl, 2-cyano-3-methyl-phenyl, 2-cyano-4-methylphenyl, 3-cyano-2-methylphenyl, 3-cyano-5-methylphenyl, 4-cyano-2-methylphenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 4-(dimethylamino)-3-methylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2-ethynyl-4-fluorophenyl, 3-fluoro-4-methoxyphenyl, 5-fluoro-2-methoxyphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-5-methylphenyl, 3-fluoro-2-methylpyphenyl, 3-fluoro-4-methylpyphenyl, 3-fluoro-5-methylphenyl, 4-fluoro-2-methylphenyl, 4-fluoro-3-methylphenyl, 5-fluoro-2-methylphenyl, 2-hydroxy-4-methylphenyl, 3-hydroxy-5-methylphenyl, 2-methoxy-3-methylphenyl, 2-methoxy-4-methylphenyl, 2-methoxy-6-methylphenyl, 3-methoxy-2-methylphenyl, 3-methoxy-4-methyl-phenyl, 3-methoxy-5-methylphenyl, 4-methoxy-2-methylphenyl, or 4-methoxy-3-methylphenyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, substituted with three substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 4-hydroxy-3,5-dimethylphenyl or 2,4,6-trimethylphenyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, substituted with four substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is phenyl, substituted with five substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic C_8-14aryl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic C_8-14, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic C_8-14, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano or halo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic C_8-14, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic C_8-14, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, methyl, isopropyl, tert-butyl, trifluoro-methyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, 1,2,4-triazol-1-yl, pyridin-4-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclopentoxy, cyclohexylmethoxy, phenoxy, 4-cyanophenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyano-benzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxy-carbonylamino, methylsulfonylamino, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclo[4.2.0]-octa-1(6),2,4-trien-3-yl, naphthalen-1-yl, naphthalen-2-yl, 5,6,7,8-tetrahydronaphthalen-1-yl, or 5,6,7,8-tetrahydronaphthalen-2-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxy-carbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclo[4.2.0]octa-1(6),2,4-trien-3-yl, naphthalen-1-yl, naphthalen-2-yl, 5,6,7,8-tetrahydronaphthalen-1-yl, or 5,6,7,8-tetrahydronaphthalen-2-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, methyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, (dimethylamino)-methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, 1,2,4-triazol-1-yl, pyridin-4-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, aminocarbonyl, methylamino-carbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclopentoxy, cyclohexylmethoxy, phenoxy, 4-cyanophenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyano-benzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxy-ethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclo[4.2.0]-octa-1(6),2,4-trien-3-yl, naphthalen-1-yl, naphthalen-2-yl, 5-(dimethylamino)-naphthalen-1-yl, 6-(dimethylamino)naphthalen-2-yl, 5,6,7,8-tetrahydro-naphthalen-1-yl, or 5,6,7,8-tetrahydro-naphthalen-2-yl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_7-15aralkyl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_7-15aralkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_7-15aralkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano or halo; (ii) C_1-6alkyl or C_1-6heteroalkyl, each optionally substituted with one or more substituents Q^a; or (iii) —OR^a, wherein R^ais as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_7-15aralkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonyl-piperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxy-carbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is C_7-15aralkyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, methyl, trifluoromethyl, or methoxy.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is benzyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is benzyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, methyl, trifluoromethyl, or methoxy.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is benzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 4-fluorobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-trifluoromethylbenzyl, 2-methoxy-benzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-phenylethyl, 3-phenylpropyl, 2-phenylprop-2-yl, 2-(3-bromophenyl)ethyl, 2-methyl-2-phenylpropyl, 2-(3-trifluoromethylphenyl)ethyl, or 2-(2-methoxyphenyl)ethyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is monocyclic heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-, 6-, or 7-membered monocyclic heteroaryl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-membered monocyclic heteroaryl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6-membered monocyclic heteroaryl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 7-membered monocyclic heteroaryl, each optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —OR^a, —NR^bR^c, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, and R^cis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methyl-pyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxycarbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-membered heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-membered heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano or halo; (ii) C_1-6alkyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —OR^aor —NR^bR^c, wherein R^a, R^b, and R^care each as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-membered heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxy-carbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-membered heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isobutyl, isopropyl, tert-butyl, trifluoro-methyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methylpyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxycarbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is furanyl, imidazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thienyl, 1,2,4-triazolyl, or tetrazolyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxy-carbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is furanyl, imidazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thienyl, 1,2,4-triazolyl, or tetrazolyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methyl-pyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxycarbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is furan-2-yl, furan-3-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, pyrrol-2-yl, pyrrol-3-yl, pyrrol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thien-2-yl, thien-3-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-4-yl, or tetrazol-5-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxy-carbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is furan-2-yl, furan-3-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, pyrrol-2-yl, pyrrol-3-yl, pyrrol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thien-2-yl, thien-3-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-4-yl, or tetrazol-5-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methylpyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxycarbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is furan-2-yl, furan-3-yl, 5-methylfuran-2-yl, 4-isopropylfuran-2-yl, 5-(morpholinomethyl)furan-2-yl, 5-(hydroxymethyl)furan-2-yl, 3-methoxy-furan-2-yl, imidazol-4-yl, 1-methylimidazol-2-yl, 1-methylimidazol-4-yl, 1-methylimidazol-5-yl, 2-methylimidazol-4-yl, 2,5-dimethylimidazol-4-yl, 2-phenylimidazol-4-yl, 4-phenylimidazol-2-yl, oxazol-2-yl, 2-methyloxazol-4-yl, 2-methyl-oxazol-5-yl, 4-methyloxazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, 1-methylpyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methylpyrazol-5-yl, 5-methylpyrazol-3-yl, 1-isopropylpyrazol-4-yl, 1-isobutyl-pyrazol-4-yl, 5-amino-1-methylpyrazol-4-yl, 4-chloro-1-methylpyrazol-3-yl, 2-cyano-1-methyl-pyrazol-4-yl, 1,4-dimethylpyrazol-5-yl, 1-phenylpyrazol-3-yl, 1-(2-methylphenyl)-pyrazol-4-yl, pyrrol-2-yl, pyrrol-3-yl, 3-cyanopyrrol-2-yl, 4-cyanopyrrol-2-yl, 1-methylpyrrol-2-yl, 3-methyl-pyrrol-2-yl, 5-methylpyrrol-2-yl, 5-(hydroxymethyl)pyrrol-2-yl, 5-(tert-butyl)pyrrol-2-yl, 2-cyano-1-methylpyrrol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 2-methylthiazol-5-yl, 4-methylthiazol-5-yl, 5-methylthiazol-2-yl, 2-cyclopropylthiazol-5-yl, 2-(morpholino)thiazol-5-yl, thien-2-yl, thien-3-yl, 2-chlorothien-3-yl, 5-chlorothien-2-yl, 5-cyanothien-2-yl, 5-cyanothien-3-yl, 3-methylthien-2-yl, 5-(dimethylamino)thien-2-yl, 5-methyl-1,2,4-triazol-3-yl, 1-(tert-butyl)-1,2,3-triazol-4-yl, 1-(1-tert-butoxycarbonylpiperidin-4-yl)-1,2,3-triazol-4-yl, or 2-methyltetrazol-5-yl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6-membered heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6-membered monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —OR^a, —NR^bR^c, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, and R^cis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6-membered heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6-membered monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, ethynyl, cyclopropyl, 4-methylphenyl, 4-methylpyridin-2-yl, pyrrolidin-1-yl, morpholino, methoxy, phenoxy, amino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is pyridinyl, 1,2-dihydropyridinyl, 1,6-dihydropyridinyl, pyridazinyl, or pyrimidinyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, tert-butyl, trifluoro-methyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromo-phenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylamino-carbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxy-carbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is pyridinyl, 1,2-dihydropyridinyl, 1,6-dihydropyridinyl, pyridazinyl, or pyrimidinyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methylpyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxy-carbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridin-5-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,6-dihydropyridin-2-yl, pyridazin-4-yl, pyrimidin-4-yl, or pyrimidin-5-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methyl-phenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 4-methylpiperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylamino-carbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxy-carbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridin-5-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydro-pyridin-4-yl, 1,6-dihydropyridin-2-yl, pyridazin-4-yl, pyrimidin-4-yl, or pyrimidin-5-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methylpyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxycarbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is chloropyrazin-2-yl, 3-methylpyrazin-2-yl, 5-methylpyrazin-2-yl, 5-methoxypyrazin-2-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 4-cyanopyridin-2-yl, 5-cyanopyridin-2-yl, 5-cyanopyridin-3-yl, 6-cyano-pyridin-2-yl, 6-cyanopyridin-3-yl, 3-fluoropyridin-4-yl, 4-fluoropyridin-2-yl, 5-fluoropyridin-2-yl, 5-fluoropyridin-3-yl, 6-fluoropyridin-2-yl, 6-fluoropyridin-3-yl, 3-chloropyridin-4-yl, 6-chloropyridin-2-yl, 2-methylpyridin-3-yl, 2-methylpyridin-4-yl, 3-methylpyridin-2-yl, 4-methyl-pyridin-2-yl, 4-methylpyridin-3-yl, 5-methylpyridin-2-yl, 5-methylpyridin-3-yl, 6-methylpyridin-2-yl, 5-isopropylpyridin-3-yl, 2-trifluoromethylpyridin-5-yl, 6-(trifluoromethyl)pyridin-3-yl, 2-(tert-butyl)pyridin-4-yl, 5-ethynylpyridin-2-yl, 6-(4-methylphenyl)pyridin-3-yl, 6-(pyrrolidin-1-yl)pyridin-3-yl, 2-(4-methylpyridin-2-yl)pyridine-4-yl, 2-hydroxypyridin-3-yl, 2-methoxy-pyridin-3-yl, 2-methoxypyridin-4-yl, 3-methoxypyridin-2-yl, 3-methoxypyridin-4-yl, 4-methoxy-pyridin-2-yl, 4-methoxypyridin-3-yl, 5-methoxypyridin-2-yl, 5-methoxypyridin-3-yl, 6-methoxy-pyridin-2-yl, 6-methoxypyridin-3-yl, 6-phenoxypyridin-3-yl, 2-aminopyridin-3-yl, 3-amino-pyridin-4-yl, 6-(methylsulfonyl)pyridin-2-yl, 2-amino-5-cyanopyridin-3-yl, 2-amino-5-methyl-pyridin-3-yl, 5-chloro-2-methoxypyridin-3-yl, 2,6-dimethylpyridin-4-yl, 5-fluoro-2-oxo-1,2-dihydropyridin-3-yl, 1-methyl-2-oxo-1,2-dihydropyridin-4-yl, 1-methyl-6-oxo-1,6-dihydro-pyridin-2-yl, pyridazin-4-yl, pyrimidin-4-yl, pyrimidin-5-yl, 2-methylpyrimidin-4-yl, 2-methyl-pyrimidin-5-yl, 2-methoxypyrimidin-4-yl, 2-(methylthio)pyrimidin-4-yl, or 2-chloro-4-(morpholino)pyrimidin-5-yl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5,5-fused, 5,6-fused, or 6,6-fused bicyclic heteroaryl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5,5-fused bicyclic heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5,6-fused bicyclic heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6,6-fused bicyclic heteroaryl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —OR^a, —NR^bR^c, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, and R^cis as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, chloro, oxo, methyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, ethynyl, cyclopropyl, phenyl, 4-methylphenyl, 4-methyl-pyridin-2-yl, pyrrolidin-1-yl, morpholino, 1-tert-butoxycarbonylpiperidin-4-yl, methoxy, phenoxy, benzoxy, amino, dimethylamino, methylthio, or methylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is benzo[d][1,3]-dioxolyl, benzofuranyl, benzo[d]imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, benzo[b]-thienyl, chromanyl, 2,3-dihydrobenzo[b][1,4]dioxinyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridinyl, 5,6-dihydroimidazo[2,1-c][1,4]oxazinyl, 3,4-dihydropyrano[2,3-c]pyridinyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyrimidinyl, indazolyl, indolyl, indolinyl, indolizinyl, isoindolinyl, isoquinolinyl, 1,8-naphthyridinyl, pyrazolo[1,5-a]pyridinyl, pyrrolo[2,3-b]-pyrazinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-b]pyridinyl, quinazolinyl, quinolinyl, quinoxalinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, thieno[2,3-b]pyridinyl, thieno[3,2-c]pyridinyl, or [1,2,4]triazolo[1,5-a]pyridinyl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, tert-butyl, trifluoro-methyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonyl-amino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromo-phenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxy-pyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonyl-piperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxy-carbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is benzo[d][1,3]-dioxol-4-yl, benzo[d][1,3]dioxol-5-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, benzo[d]imidazol-2-yl, benzo[d]imidazol-4-yl, benzo[d]imidazol-6-yl, benzo[d]oxazol-5-yl, benzo[d]oxazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]thiazol-6-yl, benzo[b]-thien-2-yl, benzo[b]-thien-3-yl, chroman-6-yl, chroman-8-yl, 2,3-dihydrobenzo[b][1,4]dioxin-6-yl, 2,3-dihydro[1,4]-dioxino[2,3-b]pyridin-6-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzo-furan-7-yl, 5,6-dihydroimidazo[2,1-c][1,4]oxazin-2-yl, 5,6-dihydroimidazo[2,1-c][1,4]oxazin-3-yl, 3,4-dihydropyrano[2,3-c]pyridin-6-yl, furo[2,3-c]pyridin-5-yl, imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-3-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,2-a]pyridin-8-yl, imidazo[1,5-a]pyridin-1-yl, imidazo[4,5-b]pyridin-2-yl, imidazo[1,2-a]pyrimidin-3-yl, imidazo[1,2-a]pyrimidin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indol-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, indol-7-yl, indolin-6-yl, indolizin-1-yl, isoindolin-2-yl, isoindolin-5-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-8-yl, 1,8-naphthyridin-2-yl, pyrazolo[1,5-a]-pyridin-3-yl, pyrazolo[1,5-a]pyridin-7-yl, pyrrolo[2,3-b]pyrazin-7-yl, pyrrolo[2,3-b]pyridin-6-yl, pyrrolo[2,3-c]pyridin-3-yl, pyrrolo[3,2-b]pyridin-3-yl, pyrrolo[3,2-b]pyridin-6-yl, quinazolin-6-yl, quinolin-4-yl, quinolin-6-yl, quinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl, quinoxalin-6-yl, 1,2,3,4-tetrahydroisoquinolin-7-yl, 1,2,3,4-tetrahydroquinolin-6-yl, thieno[2,3-b]pyridin-2-yl, thieno[3,2-c]pyridin-2-yl, or [1,2,4]triazolo[1,5-a]pyridin-7-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonyl-amino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromo-phenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxy-pyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonyl-piperidin-4-yl, 1-(tert-butoxy-carbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxy-ethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is benzo[d][1,3]-dioxol-4-yl, benzo[d][1,3]dioxol-5-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, 4-fluorobenzofuran-7-yl, benzo[d]imidazol-2-yl, benzo[d]imidazol-4-yl, 5-fluorobenzo[d]imidazol-2-yl, 1-methylbenzo[d]imidazol-2-yl, 2-hydroxybenzo[d]imidazol-6-yl, benzo[d]oxazol-5-yl, benzo[d]oxazol-6-yl, 2-methylbenzo[d]oxazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]thiazol-6-yl, benzo[b]thien-2-yl, benzo[b]thien-3-yl, chroman-6-yl, 6-fluorochroman-8-yl, 2,3-dihydro-benzo[b][1,4]dioxin-6-yl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-yl, 5,6-dihydroimidazo[2,1-c][1,4]oxazin-2-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-7-yl, 5,6-dihydroimidazo[2,1-c][1,4]oxazin-3-yl, 3,4-dihydropyrano[2,3-c]pyridin-6-yl, furo[2,3-c]pyridin-5-yl, imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-3-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,2-a]pyridin-8-yl, 2-methylimidazo[1,2-a]pyridin-3-yl, 3-methylimidazo[1,2-a]-pyridin-2-yl, 5-methylimidazo[1,2-a]pyridin-3-yl, 6-methylimidazo[1,2-a]pyridin-2-yl, 7-methylimidazo[1,2-a]pyridin-3-yl, imidazo[1,5-a]pyridin-1-yl, 1-methylimidazo[4,5-b]pyridin-2-yl, imidazo[1,2-a]pyrimidin-3-yl, imidazo[1,2-a]pyrimidin-7-yl, indazol-6-yl, 1-methyl-indazol-4-yl, 1-methylindazol-6-yl, 2-methylindazol-3-yl, 2-methylindazol-5-yl, indol-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, indol-7-yl, 6-cyanoindol-2-yl, 6-cyanoindol-3-yl, 1-methyl-indol-5-yl, 1-methylindol-6-yl, 2-methylindol-4-yl, 3-methylindol-2-yl, 4-methylindol-3-yl, 6-methylindol-3-yl, 7-methylindol-3-yl, 1-tert-butoxycarbonylindolin-6-yl, indolizin-1-yl, 1,3-dioxoisoindolin-2-yl, 1-oxoisoindolin-5-yl, 3-oxoisoindolin-5-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-8-yl, 1-chloroisoquinolin-5-yl, 1,8-naphthyridin-2-yl, pyrazolo[1,5-a]pyridin-3-yl, pyrazolo[1,5-a]pyridin-7-yl, pyrrolo[2,3-b]pyrazin-7-yl, pyrrolo[2,3-b]pyridin-6-yl, 5-methylpyrrolo[2,3-b]pyridin-3-yl, pyrrolo[2,3-c]pyridin-3-yl, pyrrolo[3,2-b]pyridin-3-yl, pyrrolo[3,2-b]pyridin-6-yl, quinazolin-6-yl, quinolin-4-yl, quinolin-6-yl, quinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl, quinoxalin-6-yl, 1,2,3,4-tetrahydro-isoquinolin-7-yl, 2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-7-yl, 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl, thieno[2,3-b]pyridin-2-yl, thieno[3,2-c]pyridin-2-yl, or [1,2,4]triazolo[1,5-a]pyridin-7-yl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 3-, 4-, 5-, 6-, or 7-membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 4-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 5-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 6-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 7-membered heterocyclyl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic bridged heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic fused heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is bicyclic spiro heterocyclyl, optionally substituted with one or more substituents Q.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is heterocyclyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently (i) cyano, halo, or oxo; (ii) C_1-6alkyl, C_1-6heteroalkyl, C_2-6alkynyl, C_3-10cycloalkyl, C_6-14aryl, C_7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q^a; or (iii) —C(O)R^a, —C(O)OR^a, —C(O)NR^bR^c, —OR^a, —NR^bR^c, —NR^aC(O)R^d, —NR^aC(O)OR^d, —NR^aS(O)₂R^d, —SR^a, or —S(O)₂R^a, wherein each R^a, R^b, R^c, and R^dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is heterocyclyl, optionally substituted with one, two, or three substituents Q, where each substituent is independently (i) C_1-6alkyl or C_7-15aralkyl, each optionally substituted with one or more substituents Q^a; or (ii) —C(O)OR^aor —S(O)₂R^a, wherein each R^ais as defined herein.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is heterocyclyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methyl-furan-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is heterocyclyl, optionally substituted with one, two, or three substituents Q, wherein each substituent is independently methyl, ethyl, benzyl, benzoxycarbonyl, tert-butoxycarbonyl, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is azetidin-3-yl, oxetan-3-yl, tetrahydropyran-4-yl, piperidin-4-yl, or piperazin-1-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxy-carbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxy-ethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl. In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is azetidin-3-yl, oxetan-3-yl, tetrahydro-pyran-4-yl, piperidin-4-yl, or piperazin-1-yl, each optionally substituted with one, two, or three substituents Q, wherein each substituent is independently methyl, ethyl, benzyl, benzoxycarbonyl, tert-butoxycarbonyl, or ethylsulfonyl.

In certain embodiments, in any one of Formulae (I) to (XIX), R⁶is 1-methyl-azetidin-3-yl, oxetan-3-yl, 3-methyloxetan-3-yl, tetrahydropyran-4-yl, ethylpiperidin-4-yl, 1-benzylpiperidin-4-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 1-(ethylsulfonyl)piperidin-4-yl, 1-(tert-butoxycarbonyl)-4-fluoropiperidin-4-yl, or 4-(tert-butoxy-carbonyl)piperazin-1-yl.

In certain embodiments, in any one of Formulae (I) to (XIX), X is —(CH₂)_n—, wherein n is an integer of 1, 2, 3, 4, or 5. In certain embodiments, in any one of Formulae (I) to (XIX), X is —CH₂—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —(CH₂)₂—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —(CH₂)₃—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —(CH₂)₄—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —(CH₂)₅—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —C(O)—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —S(O)—. In certain embodiments, in any one of Formulae (I) to (XIX), X is —S(O₂)—.

In certain embodiments, in any one of Formulae (I) to (XIX), m is an integer of 0.

All combinations of the embodiments provided herein for the groups, R¹, R², R³, R⁴, R⁵, R⁶, A, X, a, b, c, d, e, f, m, and n, in formulae described herein, including Formulae (I) to (XIX), are within the scope of this disclosure.

In one embodiment, provided herein is a compound of:

3-(6-fluoro-1-oxo-4-(1-(5,6,7,8-tetrahydronaphthalene-1-carbonyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A0001;
3-(6-fluoro-4-(1-(1-methyl-1H-indole-5-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0002;
3-(6-fluoro-1-oxo-4-(1-(quinoxaline-5-carbonyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A0003;
3-(6-fluoro-1-oxo-4-(1-(quinazoline-6-carbonyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A0004;
3-(4-(1-(2-(dimethylamino)benzoyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0005;
3-(4-(1-(4-(dimethylamino)benzoyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0006;
3-(4-(1-(2,3-dihydrobenzofuran-7-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0007;
3-(4-(1-(benzo[d]oxazole-5-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0008;
3-(4-(1-(1H-benzo[d]imidazole-7-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0009;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridine-2-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0010;
3-(4-(1-(1H-pyrrolo[3,2-b]pyridine-6-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0011;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridine-3-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0012;
3-(4-(1-(benzofuran-6-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0013;
3-(6-fluoro-1-oxo-4-(1-(2-(piperidin-1-yl)acetyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A0014;
2-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-2-oxoethyl)benzonitrile A0015;
3-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-2-oxoethyl)benzonitrile A0016;
4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-2-oxoethyl)benzonitrile A0017;
3-(4-(1-(1H-indole-7-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0018;
3-(4-(1-(1-ethylpiperidine-4-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0019;
3-(6-fluoro-1-oxo-4-(1-(2-(p-tolyl)acetyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A0020;
2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidine-1-carbonyl)benzonitrile A0021;
3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidine-1-carbonyl)benzonitrile A0022;
3-(6-fluoro-4-(1-(4-fluorobenzoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0023;
3-(6-fluoro-4-(1-(3-fluorobenzoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0024;
3-(6-fluoro-4-(1-(2-fluorobenzoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0025;
3-(6-fluoro-4-(1-(2-methylbenzoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0026;
3-(6-fluoro-4-(1-(3-methylbenzoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0027;
3-(6-fluoro-4-(1-(4-methylbenzoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0028;
3-(4-(1-(2-cyclopentylacetyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0029;
3-(4-(1-(cyclohexanecarbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0030;
3-(4-(1-(3,3-dimethylcyclobutane-1-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0031;
3-(6-fluoro-1-oxo-4-(1-(pyrimidine-5-carbonyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A0032;
3-(6-fluoro-1-oxo-4-(1-(pyridazine-4-carbonyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A0033;
3-(6-fluoro-1-oxo-4-(1-(pyrimidine-4-carbonyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A0034;
3-(6-fluoro-1-oxo-4-(1-picolinoylpiperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A0035;
3-(6-fluoro-4-(1-isonicotinoylpiperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0036;
3-(6-fluoro-4-(1-nicotinoylpiperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0037;
3-(4-(1-benzoylpiperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0038;
3-(4-(1-(1-aminocyclobutane-1-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0039;
3-(6-fluoro-4-(1-(1-methylazetidine-3-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0040;
3-(4-(1-(1H-pyrazole-5-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0041;
3-(4-(1-(1H-imidazole-5-carbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0042;
3-(6-Fluoro-4-(1-(furan-3-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0043;
3-(6-fluoro-4-(1-(furan-2-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0044;
3-(6-fluoro-4-(1-(1-fluorocyclopropane-1-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0045;
3-(6-fluoro-4-(1-(3-methylbutanoyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0046;
3-(6-fluoro-4-(1-(oxetane-3-carbonyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0047;
3-(4-(1-(cyclobutanecarbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0048;
3-(6-fluoro-4-(1-(methylglycyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A0049; or
3-(4-(1-(cyclopropanecarbonyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A0050;

or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

In another embodiment, provided herein is a compound of:

3-(4-(1-(cyclobutylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1001;
3-(4-(1-((1H-pyrrol-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1002;
3-(4-(1-((1H-pyrrol-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1003;
3-(4-(1-((1H-imidazol-5-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1004;
3-(4-(1-((1H-pyrazol-5-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1005;
3-(6-fluoro-4-(1-(oxazol-2-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1006;
3-(6-fluoro-4-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1007;
3-(6-fluoro-4-(1-(3-hydroxy-2,2-dimethylpropyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1008;
3-(6-fluoro-1-oxo-4-(1-(pyridin-3-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1009;
3-(6-fluoro-1-oxo-4-(1-(pyridin-2-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1010;
3-(6-fluoro-1-oxo-4-(1-(pyrimidin-5-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1011;
3-(6-fluoro-4-(1-((1-methyl-1H-pyrrol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1012;
3-(6-fluoro-4-(1-((5-methyl-1H-pyrrol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1013;
3-(6-fluoro-4-(1-((3-methyl-1H-pyrrol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1014;
3-(6-fluoro-4-(1-((5-methylfuran-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1015;
3-(6-fluoro-4-(1-((5-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1016;
3-(6-fluoro-4-(1-((1-methyl-1H-imidazol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1017;
3-(6-fluoro-4-(1-((1-methyl-1H-imidazol-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1018;
3-(6-fluoro-4-(1-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1019;
3-(6-fluoro-4-(1-((1-methyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1020;
3-(6-fluoro-4-(1-((1-methyl-1H-imidazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1021;
3-(6-fluoro-4-(1-((2-methyloxazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1022;
3-(6-fluoro-4-(1-((2-methyloxazol-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1023;
3-(6-fluoro-4-(1-((4-methyloxazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1024;
3-(6-fluoro-4-(1-((5-methyl-4H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1025;
3-(6-fluoro-4-(1-((2-methyl-2H-tetrazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1026;
3-(6-fluoro-1-oxo-4-(1-(thiophen-3-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1027;
3-(6-fluoro-1-oxo-4-(1-(thiophen-2-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1028;
3-(6-fluoro-1-oxo-4-(1-(thiazol-4-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1029;
3-(6-fluoro-1-oxo-4-(1-(thiazol-5-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1030;
3-(6-fluoro-1-oxo-4-(1-(thiazol-2-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1031;
3-(6-fluoro-1-oxo-4-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1032;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-1H-pyrrole-3-carbonitrile A1033;
3-(6-fluoro-4-(1-(3-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1034;
3-(6-fluoro-1-oxo-4-(1-phenethylpiperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1035;
3-(6-fluoro-4-(1-(2-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1036;
3-(6-fluoro-4-(1-(4-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1037;
3-(4-(1-(2-aminobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1038;
3-(4-(1-(4-aminobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1039;
3-(6-fluoro-4-(1-((5-methylpyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1040;
3-(6-fluoro-4-(1-((4-methylpyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1041;
3-(6-fluoro-4-(1-((6-methylpyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1042;
3-(6-fluoro-4-(1-((5-methylpyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1043;
3-(6-fluoro-4-(1-((2-methylpyridin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1044;
3-(6-fluoro-4-(1-((2-methylpyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1045;
3-(6-fluoro-4-(1-((3-methylpyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1046;
3-(6-fluoro-4-(1-((4-methylpyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1047;
3-(6-fluoro-4-(1-(4-hydroxybenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1048;
3-(6-fluoro-4-(1-(3-hydroxybenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1049;
3-(4-(1-((3-aminopyridin-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1050;
3-(4-(1-((2-aminopyridin-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1051;
3-(6-fluoro-4-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1052;
3-(6-fluoro-4-(1-((2-Methylpyrimidin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1053;
3-(6-fluoro-4-(1-((3-methylpyrazin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1054;
3-(6-fluoro-4-(1-((5-methylpyrazin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1055;
3-(6-fluoro-4-(1-((2-hydroxypyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1056;
3-(6-fluoro-4-(1-(3-fluorobenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1057;
3-(6-fluoro-4-(1-(4-fluorobenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1058;
3-(4-(1-((1,4-dimethyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1059;
3-(4-(1-((2,5-dimethyl-1H-imidazol-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1060;
3-(6-fluoro-4-(1-((6-fluoropyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1061;
3-(6-fluoro-4-(1-((4-fluoropyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1062;
3-(6-fluoro-4-(1-((5-fluoropyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1063;
3-(6-fluoro-4-(1-((5-fluoropyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1064;
3-(6-fluoro-4-(1-((3-fluoropyridin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1065;
3-(6-fluoro-4-(1-((6-fluoropyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1066;
3-(6-fluoro-4-(1-((5-(hydroxymethyl)-1H-pyrrol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1067;
3-(4-(1-((5-amino-1-methyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1068;
3-(6-fluoro-4-(1-((5-(hydroxymethyl)furan-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1069;
3-(6-fluoro-4-(1-((3-methoxyfuran-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1070;
3-(6-fluoro-4-(1-((3-methylthiophen-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1071;
3-(4-(1-(2-cyclohexylethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1072;
3-(6-fluoro-4-(1-((4-methylthiazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1073;
3-(6-fluoro-4-(1-((2-methylthiazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1074;
3-(6-fluoro-4-(1-((5-methylthiazol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1075;
3-(4-(1-(3-ethynylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1076;
3-(4-(1-(2-ethynylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1077;
3-(4-(1-(4-ethynylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1078;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)benzonitrile A1079;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)benzonitrile A1080;
3-(4-(1-((5-ethynylpyridin-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1081;
3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)benzonitrile A1082;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)isonicotinonitrile A1083;
6-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)picolinonitrile A1084;
5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)nicotinonitrile A1085;
5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)picolinonitrile A1086;
3-(4-(1-(bicyclo[4.2.0]octa-1(6),2,4-trien-3-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1087;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-1-methyl-1H-pyrrole-2-carbonitrile A1088;
3-(6-fluoro-1-oxo-4-(1-(3-phenylpropyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1089;
3-(4-(1-(3,5-dimethylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1090;
3-(6-fluoro-4-(1-(2-methylphenethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1091;
3-(4-(1-(2,5-dimethylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1092;
3-(4-(1-(2,4-dimethylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1093;
3-(4-(1-(2,6-dimethylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1094;
3-(6-fluoro-4-(1-(2-(methylamino)benzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1095;
3-(4-(1-((2,6-dimethylpyridin-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1096;
3-(6-fluoro-4-(1-(4-(hydroxymethyl)benzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1097;
3-(6-fluoro-4-(1-(2-hydroxy-4-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1098;
3-(6-fluoro-4-(1-(3-methoxybenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1099;
3-(6-fluoro-4-(1-(3-hydroxy-5-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1100;
3-(6-fluoro-4-(1-(4-methoxybenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1101;
3-(6-fluoro-4-(1-(2-methoxybenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1102;
3-(4-(1-((2-amino-5-methylpyridin-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1103;
3-(6-fluoro-4-(1-((1-methyl-2-oxo-1,2-dihydropyridin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1104;
3-(6-fluoro-4-(1-((1-methyl-6-oxo-1,6-dihydropyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1105;
3-(6-fluoro-4-(1-((5-methoxypyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1106;
3-(6-fluoro-4-(1-((6-methoxypyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1107;
3-(6-fluoro-4-(1-((4-methoxypyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1108;
3-(6-fluoro-4-(1-((3-methoxypyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1109;
3-(6-fluoro-4-(1-((5-methoxypyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1110;
3-(6-fluoro-4-(1-((4-methoxypyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1111;
3-(6-fluoro-4-(1-((6-methoxypyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1112;
3-(6-fluoro-4-(1-((3-methoxypyridin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1113;
3-(6-fluoro-4-(1-((2-methoxypyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1114;
3-(6-fluoro-4-(1-((2-methoxypyridin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1115;
5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)thiophene-2-carbonitrile A1116;
3-(6-fluoro-4-(1-((2-methoxypyrimidin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1117;
3-(6-fluoro-4-(1-((5-methoxypyrazin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1118;
3-(6-fluoro-4-(1-(5-fluoro-2-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1119;
3-(6-fluoro-4-(1-(4-fluoro-2-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1120;
3-(6-fluoro-4-(1-(3-fluoro-5-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1121;
3-(6-fluoro-4-(1-(4-fluoro-3-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1122;
3-(6-fluoro-4-(1-(2-fluoro-5-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1123;
3-(6-fluoro-4-(1-(3-fluoro-2-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1124;
3-(6-fluoro-4-(1-(4-fluorophenethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1125;
3-(6-fluoro-4-(1-(3-(5-methylfuran-2-yl)propyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1126;
3-(6-fluoro-4-(1-((4-isopropylfuran-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1127;
3-(6-fluoro-4-(1-((1-isopropyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1128;
3-(4-(1-(2-amino-5-fluorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1129;
3-(4-(1-(3-chlorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1130;
3-(4-(1-(4-chlorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1131;
3-(4-(1-(2-chlorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1132;
3-(6-fluoro-4-(1-((5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1133;
3-(4-(1-((6-chloropyridin-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1134;
3-(4-(1-((3-chloropyridin-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1135;
3-(4-(1-((3-chloropyrazin-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1136;
3-(4-(1-((4-chloro-1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1137;
3-(4-(1-((1H-indol-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1138;
3-(4-(1-((1H-indol-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1139;
3-(4-(1-((1H-indol-7-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1140;
3-(6-fluoro-4-(1-(indolizin-1-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1141;
3-(4-(1-((1H-indol-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1142;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-3-methylbenzonitrile A1143;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-6-methylbenzonitrile A1144;
3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-5-methylbenzonitrile A1145;
3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-2-methylbenzonitrile A1146;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-5-methylbenzonitrile A1147;
3-(4-(1-(benzofuran-5-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1148;
3-(4-(1-(benzofuran-7-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1149;
3-(4-(1-(benzofuran-4-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1150;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridin-2-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1151;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridin-3-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1152;
3-(4-(1-((1H-benzo[d]imidazol-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1153;
3-(4-(1-((1H-pyrrolo[3,2-b]pyridin-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1154;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridin-7-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1155;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridin-8-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1156;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridin-6-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1157;
3-(4-(1-((1H-benzo[d]imidazol-7-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1158;
3-(4-(1-((1H-pyrrolo[2,3-b]pyridin-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1159;
3-(6-fluoro-4-(1-(imidazo[1,5-a]pyridin-1-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1160;
3-(4-(1-((1H-pyrrolo[3,2-b]pyridin-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1161;
3-(4-(1-((2H-indazol-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1162;
3-(6-fluoro-1-oxo-4-(1-(pyrazolo[1,5-a]pyridin-3-ylmethyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1163;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyridin-5-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1164;
3-(4-(1-((1H-pyrrolo[2,3-c]pyridin-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1165;
3-(6-fluoro-1-oxo-4-(1-(pyrazolo[1,5-a]pyridin-7-ylmethyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1166;
3-(4-(1-(2-cyclopropylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1167;
3-(4-(1-(4-cyclopropylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1168;
3-(4-(1-((2-chlorothiophen-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1169;
3-(4-(1-((5-chlorothiophen-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1170;
3-(4-(1-(benzo[d]oxazol-6-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1171;
3-(4-(1-(benzo[d]oxazol-5-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1172;
3-(6-fluoro-4-(1-(furo[2,3-c]pyridin-5-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1173;
5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)-2-hydroxybenzonitrile A1174;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-3-hydroxybenzonitrile A1175;
3-(4-(1-((4H-pyrrolo[2,3-b]pyrazin-7-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1176;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyrimidin-7-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1177;
6-amino-5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)methyl)nicotinonitrile A1178;
3-(6-fluoro-4-(1-(imidazo[1,2-a]pyrimidin-3-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1179;
3-(4-(1-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1180;
3-(4-(1-(2-ethynyl-4-fluorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1181;
3-(4-(1-((4,4-difluorocyclohexyl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1182;
3-(6-fluoro-1-oxo-4-(1-(4-phenylbutyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1183;
3-(6-fluoro-4-(1-(4-isopropylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1184;
3-(6-fluoro-1-oxo-4-(1-(2,4,6-trimethylbenzyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1185;
5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-2-fluorobenzonitrile A1186;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-2-fluorobenzonitrile A1187;
3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-5-fluorobenzonitrile A1188;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-3-fluorobenzonitrile A1189;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-5-fluorobenzonitrile A1190;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-4-fluorobenzonitrile A1191;
3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)benzamide A1192;
3-(4-(1-(3-(dimethylamino)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1193;
3-(4-(1-(4-(ethylamino)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1194;
3-(6-fluoro-4-(1-((5-isopropylpyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1195;
3-(4-(1-(2-(dimethylamino)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1196;
3-(4-(1-(benzo[d][1,3]dioxol-4-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1197;
3-(4-(1-(2-(benzyloxy)ethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1198;
3-(6-fluoro-4-(1-(2-methoxy-4-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1199;
3-(6-fluoro-4-(1-(3-methoxy-4-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1200;
3-(4-(1-(4-ethoxybenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1201;
3-(6-fluoro-4-(1-(4-hydroxy-3,5-dimethylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1202;
3-(6-fluoro-4-(1-(4-methoxy-2-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1203;
3-(6-fluoro-4-(1-(3-methoxyphenethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1204;
3-(6-fluoro-4-(1-(4-methoxyphenethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1205;
3-(6-fluoro-4-(1-(3-methoxy-5-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1206;
3-(6-fluoro-4-(1-(2-methoxy-6-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1207;
3-(6-fluoro-4-(1-(3-methoxy-2-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1208;
3-(6-fluoro-4-(1-(2-methoxy-3-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1209;
3-(6-fluoro-4-(1-(4-methoxy-3-methylbenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1210;
3-(4-(1-((2-(dimethylamino)pyrimidin-5-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1211;
3-(4-(1-((5-(tert-butyl)-1H-pyrrol-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1212;
3-(4-(1-((5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazin-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1213;
3-(4-(1-((5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazin-3-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1214;
3-(6-fluoro-4-(1-((1-isobutyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1215;
3-(4-(1-((1-(tert-butyl)-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1216;
3-(4-(1-((2-cyclopropylthiazol-5-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1217;
3-(6-fluoro-4-(1-((2-(methylthio)pyrimidin-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1218;
3-(6-fluoro-4-(1-((4-hydroxybicyclo[2.2.2]octan-1-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1219;
3-(4-(1-(4-chlorophenethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1220;
3-(4-(1-((5-(dimethylamino)thiophen-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1221;
3-(4-(1-(2-amino-3-chlorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1222;
3-(4-(1-(2-amino-4-chlorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1223;
3-(4-(1-(2-amino-6-chlorobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1224;
3-(6-fluoro-4-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1225;
3-(6-fluoro-1-oxo-4-(1-(quinolin-6-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1226;
3-(6-fluoro-1-oxo-4-(1-(quinolin-4-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1227;
3-(6-fluoro-4-(1-(isoquinolin-5-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1228;
3-(6-fluoro-4-(1-(isoquinolin-8-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1229;
3-(6-fluoro-4-(1-(isoquinolin-3-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1230;
3-(6-fluoro-4-(1-(isoquinolin-4-ylmethyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1231;
3-(6-fluoro-1-oxo-4-(1-(quinolin-8-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1232;
3-(6-fluoro-1-oxo-4-(1-(quinoxalin-5-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1233;
3-(6-fluoro-1-oxo-4-(1-(quinoxalin-2-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1234;
3-(4-(1-((1,8-naphthyridin-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1235;
3-(6-fluoro-1-oxo-4-(1-(quinoxalin-6-ylmethyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1236;
tert-butyl (2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)ethyl)carbamate A1237;
3-(6-fluoro-4-(1-((6-methyl-1H-indol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1238;
3-(6-fluoro-4-(1-((3-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1239;
3-(6-fluoro-4-(1-((4-methyl-1H-indol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1240;
3-(6-fluoro-4-(1-((1-methyl-1H-indol-6-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1241;
3-(6-fluoro-4-(1-((2-methyl-1H-indol-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1242;
3-(6-fluoro-4-(1-((1-methyl-1H-indol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1243;
3-(6-fluoro-4-(1-((7-methyl-1H-indol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1244;
3-(6-fluoro-4-(1-((2-methyl-2H-indazol-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1245;
3-(6-fluoro-4-(1-((2-methylimidazo[1,2-a]pyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1246;
3-(6-fluoro-4-(1-((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1247;
3-(6-fluoro-4-(1-((5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1248;
3-(6-fluoro-4-(1-((1-methyl-1H-indazol-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1249;
3-(6-fluoro-4-(1-((7-methylimidazo[1,2-a]pyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1250;
3-(6-fluoro-4-(1-((5-methylimidazo[1,2-a]pyridin-3-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1251;
3-(6-fluoro-4-(1-((6-methylimidazo[1,2-a]pyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1252;
3-(6-fluoro-4-(1-((2-methyl-2H-indazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1253;
3-(6-fluoro-4-(1-((1-methyl-1H-indazol-6-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1254;
3-(6-fluoro-4-(1-((3-methylimidazo[1,2-a]pyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1255;
3-(6-fluoro-1-oxo-4-(1-((5,6,7,8-tetrahydronaphthalen-1-yl)methyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1256;
3-(6-fluoro-1-oxo-4-(1-((1-oxoisoindolin-5-yl)methyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1257;
3-(6-fluoro-1-oxo-4-(1-((3-oxoisoindolin-5-yl)methyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1258;
3-(6-fluoro-4-(1-((2-methylbenzo[d]oxazol-6-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1259;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-5-methoxybenzonitrile A1260;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-3-methoxybenzonitrile A1261;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-2-methoxybenzonitrile A1262;
3-(6-fluoro-4-(1-((1-methyl-1H-imidazo[4,5-b]pyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1263;
3-(4-(1-(chroman-6-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1264;
3-(4-(1-(benzo[b]thiophen-2-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1265;
3-(4-(1-(benzo[b]thiophen-3-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1266;
3-(6-fluoro-4-(1-(3-methyl-3-phenylbutyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1267;
3-(4-(1-((3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1268;
3-(6-fluoro-1-oxo-4-(1-(thieno[2,3-b]pyridin-2-ylmethyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1269;
3-(4-(1-(benzo[d]thiazol-4-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1270;
3-(6-fluoro-1-oxo-4-(1-(thieno[3,2-c]pyridin-2-ylmethyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1271;
3-(4-(1-(4-((dimethylamino)methyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1272;
3-(4-(1-((2-(tert-butyl)pyridin-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1273;
3-(4-(1-(4-(dimethylamino)-3-methylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1274;
3-(6-fluoro-4-(1-((4-fluorobenzofuran-7-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1275;
3-(6-fluoro-4-(1-((5-fluoro-1H-benzo[d]imidazol-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1276;
3-(4-(1-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1277;
3-(6-fluoro-4-(1-(3-(2-methoxyphenyl)propyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1278;
3-(4-(1-(3-(benzyloxy)propyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1279;
3-(4-(1-((adamantan-1-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1280;
3-(4-(1-((2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1281;
3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-1H-indole-6-carbonitrile A1282;
2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-1H-indole-6-carbonitrile A1283;
3-(4-(1-(4-(1H-pyrazol-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1284;
3-(4-(1-(4-(1H-imidazol-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1285;
3-(6-fluoro-1-oxo-4-(1-((2-phenyl-1H-imidazol-5-yl)methyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1286;
3-(4-(1-(3-(1H-imidazol-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1287;
3-(6-fluoro-1-oxo-4-(1-((5-phenyl-1H-imidazol-2-yl)methyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1288;
3-(6-fluoro-1-oxo-4-(1-((1-phenyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1289;
3-(4-(1-(4-(1H-1,2,4-triazol-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1290;
3-(4-(1-(2-(1H-1,2,4-triazol-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1291;
3-(4-(1-(3-(1H-1,2,4-triazol-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1292;
3-(6-fluoro-1-oxo-4-(1-(4-(pyrrolidin-1-yl)benzyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1293;
3-(6-fluoro-1-oxo-4-(1-(3-(pyrrolidin-1-yl)benzyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1294;
3-(6-fluoro-1-oxo-4-(1-((6-(pyrrolidin-1-yl)pyridin-3-yl)methyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1295;
3-(6-fluoro-4-(1-((6-fluorochroman-8-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1296;
3-(4-(1-([1,1′-biphenyl]-4-ylmethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1297;
3-(6-fluoro-1-oxo-4-(1-(3-(pyridin-4-yl)benzyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1298;
3-(6-fluoro-4-(1-((6-(methylsulfonyl)pyridin-2-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1299;
3-(6-fluoro-1-oxo-4-(1-(3-(quinolin-6-yl)propyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1300;
3-(6-fluoro-4-(1-(4-morpholinobenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1301;
3-(6-fluoro-4-(1-(3-morpholinobenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1302;
3-(6-fluoro-4-(1-(2-morpholinobenzyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1303;
4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-N-isopropylbenzamide A1304;
3-(6-fluoro-1-oxo-4-(1-((6-(p-tolyl)pyridin-3-yl)methyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1305;
3-(6-fluoro-1-oxo-4-(1-(3-phenoxybenzyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1306;
3-(6-fluoro-1-oxo-4-(1-(4-phenoxybenzyl)piperidin-4-yl)isoindolin-2-yl)-piperidine-2,6-dione A1307;
3-(6-fluoro-4-(1-((4′-methyl-[2,2′-bipyridin]-4-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1308;
3-(4-(1-(4-(ethylsulfonyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1309;
3-(6-fluoro-4-(1-((2-morpholinothiazol-5-yl)methyl)piperidin-4-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1310;
3-(4-(1-(4-bromophenethyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1311;
3-(6-fluoro-1-oxo-4-(1-(2-(pyridin-2-yloxy)benzyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione A1312;
N-(3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)phenyl)methanesulfonamide A1313;
N-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)phenyl)methanesulfonamide A1314;
N-(2-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)phenyl)methanesulfonamide A1315;
3-(4-(1-((6-(dimethylamino)naphthalen-2-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1316;
3-(6-fluoro-1-oxo-4-(1-(3-(3-(trifluoromethyl)phenyl)propyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1317;
2-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)propyl)isoindoline-1,3-dione A1318;
3-(4-(1-((1-benzylpiperidin-4-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1319;
3-(4-(1-(2-chloro-5-(trifluoromethyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1320;
3-(4-(1-(5-chloro-2-(trifluoromethyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1321;
3-(4-(1-(4-chloro-2-(trifluoromethyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1322;
3-(4-(1-(2-chloro-4-(trifluoromethyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1323;
3-(4-(1-(3-chloro-4-(trifluoromethyl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1324;
5-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)-methyl)-2-(4-methyl-1H-imidazol-1-yl)benzonitrile A1325;
3-(4-(1-(3-(benzyloxy)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1326;
3-(4-(1-(4-(benzyloxy)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)-piperidine-2,6-dione A1327;
3-(4-(1-(3-(3-bromophenyl)propyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1328;
3-(4-(1-(3-(cyclohexylmethoxy)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1329;
4-(3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)phenoxy)benzonitrile A1330;
4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)phenoxy)benzonitrile A1331;
3-(4-(1-(3-chloro-4-morpholinobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1332;
3-(4-(1-(4-(benzyloxy)-2-methylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1333;
3-(4-(1-(2-(benzyloxy)-4-methylbenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1334;
tert-butyl 4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)ethyl)piperidine-1-carboxylate A1335;
tert-butyl ((1r,4r)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)cyclohexyl)carbamate A1336;
3-(4-(1-((2-chloro-4-morpholinopyrimidin-5-yl)methyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1337;
tert-butyl 4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)ethyl)piperazine-1-carboxylate A1338;
tert-butyl 4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)-4-fluoropiperidine-1-carboxylate A1339;
4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)phenoxy)-3-fluorobenzonitrile A1340;
tert-butyl (((1r,4r)-4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)piperidin-1-yl)methyl)cyclohexyl)methyl)carbamate A1341;
tert-butyl 6-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)methyl)indoline-1-carboxylate A1342;
benzyl (4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)methyl)phenyl)carbamate A1343;
tert-butyl 4-(1-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)-2-methylpropan-2-yl)piperidine-1-carboxylate A1344;
3-(4-(1-(4-(benzyloxy)-3-ethoxybenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1345;
3-(6-fluoro-1-oxo-4-(1-(4-(4-(trifluoromethyl)phenoxy)benzyl)piperidin-4-yl)-isoindolin-2-yl)piperidine-2,6-dione A1346;
3-(4-(1-(3-bromo-4-morpholinobenzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1347;
tert-butyl 4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate A1348;
3-(4-(1-(3-bromo-4-(4-methylpiperazin-1-yl)benzyl)piperidin-4-yl)-6-fluoro-1-oxoisoindolin-2-yl)piperidine-2,6-dione A1349; or
4-(4-bromo-3-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)-piperidin-1-yl)methyl)phenoxy)benzonitrile A1350;

or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.