GAMMA SECRETASE MODULATORS

FIELD OF THE INVENTION

The present invention relates to certain heterocyclic compounds useful as gamma secretase modulators (including inhibitors, antagonists and the like), pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat various diseases including central nervous system disorders such as, for example, neurodegenerative diseases such as Alzheimer's disease and other diseases relating to the deposition of amyloid protein. They are especially useful for reducing Amyloid beta (hereinafter referred to as Aβ) production which is effective in the treatment of diseases caused by Aβ such as, for example, Alzheimers and Down Syndrome.

BACKGROUND OF THE INVENTION

Alzheimer's disease is a disease characterized by degeneration and loss of neurons and also by the formation of senile plaques and neurofibrillary change. Presently, treatment of Alzheimer's disease is limited to symptomatic therapies with a symptom-improving agent represented by an acetylcholinesterase inhibitor, and the basic remedy which prevents progress of the disease has not been developed. A method of controlling the cause of onset of pathologic conditions needs to be developed for creation of the basic remedy of Alzheimer's disease.

Aβ protein, which is a metabolite of amyloid precursor protein (hereinafter referred to as APP), is considered to be greatly involved in degeneration and loss of neurons as well as onset of demential conditions (for example, see Klein W L, et al Proceeding National Academy of Science USA, Sep. 2, 2003, 100(18), p. 10417-22, suggest a molecular basis for reversible memory loss).

Nitsch R M, and 16 others, Antibodies against β-amyloid slow cognitive decline in Alzheimer's disease, Neuron, May 22, 2003, 38(4), p. 547-554) suggest that the main components of Aβ protein are Aβ40 consisting of 40 amino acids and Aβ42 having two additional amino acids at the C-terminal. The Aβ40 and Aβ42 tend to aggregate (for example, see Jarrell J T et al, The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease, Biochemistry, May 11, 1993, 32(18), p. 4693-4697) and constitute main components of senile plaques (for example, (Glenner G G, et al, Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein, Biochemical and Biophysical Research Communications, May 16, 1984, 120(3), p. 885-90. See also Masters C L, et al, Amyloid plaque core protein in Alzheimer disease and Down syndrome, Proceeding National Academy of Science USA, June 1985, 82(12), p. 4245-4249.).

Furthermore, it is known that mutations of APP and presenelin genes, which is observed in familial Alzheimer's disease, increase production of Aβ40 and Aβ42 (for example, see Gouras G K, et al, Intraneuronal Aβ42 accumulation in human brain, American Journal of Pathology, January 2000, 156(1), p. 15-20. Also, see Scheuner D, et al, Nature Medicine, August 1996, 2(8), p. 864-870; and Forman M S, et al, Differential effects of the Swedish mutant amyloid precursor protein on β-amyloid accumulation and secretion in neurons and nonneuronal cells, Journal of Biological Chemistry, Dec. 19, 1997, 272(51), p. 32247-32253.). Therefore, compounds which reduce production of Aβ40 and Aβ42 are expected as an agent for controlling progress of Alzheimer's disease or for preventing the disease.

These Aβs are produced when APP is cleaved by beta secretase and subsequently clipped by gamma secretase. In consideration of this, creation of inhibitors of γ secretase and β secretase has been attempted for the purpose of reducing production of Aβs. Many of these secretase inhibitors already known are peptides or peptidomimetics such as L-685,458. L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid β-protein precursor γ-secretase activity, Biochemistry, Aug. 1, 2000, 39(30), p. 8698-8704).

Also of interest in connection with the present invention are: US 2007/0117798 (Eisai, published May 24, 2007); US 2007/0117839 (Eisai, published May 24, 2007); US 2006/0004013 (Eisai, published Jan. 5, 2006); WO 2005/110422 (Boehringer Ingelheim, published Nov. 24, 2005); WO 2006/045554 (Cellzone AG, published May 4, 2006); WO 2004/110350 (Neurogenetics, published Dec. 23, 2004); WO 2004/071431 (Myriad Genetics, published Aug. 26, 2004); US 2005/0042284 (Myriad Genetics, published Feb. 23, 2005) and WO 2006/001877 (Myriad Genetics, published Jan. 5, 2006).

There is a need for new compounds, formulations, treatments and therapies to treat diseases and disorders associated with Aβ. It is, therefore, an object of this invention to provide compounds useful in the treatment or prevention or amelioration of such diseases and disorders.

SUMMARY OF THE INVENTION

In its many embodiments, the present invention provides a novel class of heterocyclic compounds as gamma secretase modulators (including inhibitors, antagonists and the like), methods of preparing such compounds, pharmaceutical compositions comprising one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition or amelioration of one or more diseases associated with the Aβ using such compounds or pharmaceutical compositions.

The compounds of this invention (Formula (I)) can be useful as gamma secretase modulators and can be useful in the treatment and prevention of diseases such as, for example, Alzheimers disease, mild cognitive impairment (MCI), Downs Syndrome, Glaucoma (Guo et. al., Proc. Natl. Acad. Sci. USA 104, 13444-13449 (2007)), Cerebral amyloid angiopathy, stroke or dementia (Frangione et al., Amyloid: J. Protein folding Disord. 8, suppl. 1, 36-42 (2001), Microgliosis and brain inflammation (M P Lamber, Proc. Natl. Acad. Sci. USA 95, 6448-53 (1998)), Olfactory function loss (Getchell, et. al. Neurobiology of Aging, 663-673, 24; 2003).

Thus, this invention provides compounds of the formula:

or a pharmaceutically acceptable salt, ester, solvate or prodrug thereof, wherein R¹, R², R⁸, R⁹, R¹⁰, R¹², U, W and X are each independently selected and are as defined below.

The compounds of Formula (I) can be useful as gamma secretase modulators and can be useful in the treatment and prevention of diseases such as, for example, central nervous system disorders such as Alzheimers disease and Downs Syndrome.

This invention also provides compounds of formula (I).

This invention also provides pharmaceutically acceptable salts of the compounds of formula (I).

This invention also provides pharmaceutically acceptable esters of the compounds of formula (I).

This invention also provides solvates of the compounds of formula (I).

This invention also provides compounds of formula (I) in pure and isolated form.

This invention also provides compounds of formula (I) in pure form.

This invention also provides compounds of formula (I) in isolated form.

This invention also provides compounds Y1, Y2, Y3, A9-A14, B1-B15, C3-C5, D4, E4, E6-E9, F7-F19, F20d-F20h, F21d-F21h, F22d-F22h, F23c-F23h, F24c-F24h, F25a-F25h, F26a-F26h, F27a-F27h, F28a-F28h, F29a-F29h, F30a-F30h, F31a-F31h, F32a-F32h, F33a-F33h, J1, J2, K7, K8b-K8h, K9a-K9h, K10a-K10h, K11a-K11h, K12a-K12h, K13a-K13h, K14a-K14h, K15a-K15h, K16a-K16h, K17a-K17h, K18a-K18h, K19a-K19h, K20a-K20h, K21a-K21h, K22a-K22h, and X1-X11.

This invention also provides compounds (R)-A9, (R)-B7, F7-F13, J1, (S)-A9, (S)-B7, F14-F19, J2, A10, B8, B15 and D3.

This invention also provides pharmaceutical compositions comprising an effective amount of one or more (e.g., one) compounds of formula (I), or a pharmaceutically acceptable salt, ester or solvate thereof, and an effective amount of one or more (e.g., one) other pharmaceutically active ingredients (e.g., drugs), and a pharmaceutically acceptable carrier.

This invention also provides a method for modulating (including inhibiting, antagonizing and the like) gamma-secretase, comprising administering an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I) to a patient in need of treatment.

This invention also provides a method for modulating (including inhibiting, antagonizing and the like) gamma-secretase, comprising administering an effective (i.e., therapeutically effective) amount of a compound of formula (I) to a patient in need of treatment.

This invention also provides a method of treating one or more neurodegenerative diseases, comprising administering an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating one or more neurodegenerative diseases, comprising administering an effective (i.e., therapeutically effective) amount of a compound of formula (I) to a patient in need of treatment.

This invention also provides a method of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain), comprising administering an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain), comprising administering an effective (i.e., therapeutically effective) amount of a compound of formula (I) to a patient in need of treatment.

This invention also provides a method of treating Alzheimer's disease, comprising administering an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I), in combination with an effective (i.e., therapeutically effective) amount of one or more cholinesterase inhibitors (such as, for example, (±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride, i.e., donepezil hydrochloride, available as the Aricept® brand of donepezil hydrochloride), to a patient in need of treatment.

This invention also provides a method of treating Alzheimer's disease, comprising administering an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I), in combination with an effective (i.e., therapeutically effective) amount of one or more compounds selected from the group consisting of Aβ antibody inhibitors, gamma secretase inhibitors and beta secretase inhibitors.

This invention also provides combinations comprising an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I), in combination with an effective (i.e., therapeutically effective) amount of one or more compounds selected from the group consisting of cholinesterase inhibitors (such as, for example, (±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride, i.e., donepezil hydrochloride, available as the Aricept® brand of donepezil hydrochloride), Aβ antibody inhibitors, gamma secretase inhibitors and beta secretase inhibitors.

This invention also provides a method of treating Alzheimer's disease, comprising administering an effective (i.e., therapeutically effective) amount of a compound of formula (I), in combination with an effective (i.e., therapeutically effective) amount of one or more (e.g., one) cholinesterase inhibitors (such as, for example, (±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride, i.e., donepezil hydrochloride, available as the Aricept® brand of donepezil hydrochloride), to a patient in need of treatment.

This invention also provides a method of treating Downs syndrome, comprising administering an effective (i.e., therapeutically effective) amount of one or more compounds of formula (I), in combination with an effective (i.e., therapeutically effective) amount of one or more cholinesterase inhibitors (such as, for example, (±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride, i.e., donepezil hydrochloride, available as the Aricept® brand of donepezil hydrochloride), to a patient in need of treatment.

This invention also provides a method of treating Downs syndrome, comprising administering an effective (i.e., therapeutically effective) amount of a compound of formula (I), in combination with an effective (i.e., therapeutically effective) amount of one or more (e.g., one) cholinesterase inhibitors (such as, for example, (±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride, i.e., donepezil hydrochloride, available as the Aricept® brand of donepezil hydrochloride), to a patient in need of treatment.

This invention also provides combination therapies for (1) modulating gamma-secretase, or (2) treating one or more neurodegenerative diseases, or (3) inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain), or (4) treating Alzheimer's disease. The combination therapies are directed to methods comprising the administration of an effective amount of one or more (e.g. one) compounds of formula (I) and the administration of an effective amount of one or more (e.g., one) other pharmaceutical active ingredients (e.g., drugs).

This invention also provides a method of treating mild cognitive impairment, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating glaucoma, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating cerebral amyloid angiopathy, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating stroke, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating dementia, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating microgliosis, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating brain inflammation, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides a method of treating olfactory function loss, comprising administering an effective amount of one or more (e.g., one) compounds of formula (I) to a patient in need of treatment.

This invention also provides pharmaceutical compositions comprising a combination of an effective amount of one or more (e.g., one) compounds of formula (I), in combination with an effective amount of one or more compounds selected from the group consisting of cholinesterase inhibitors, Aβ antibody inhibitors, gamma secretase inhibitors and beta secretase inhibitors. The pharmaceutical compositions also comprise a pharmaceutically acceptable carrier.

This invention also provides a kit comprising, in separate containers, in a single package, pharmaceutical compositions for use in combination, wherein one container comprises an effective amount of a compound of formula (I) in a pharmaceutically acceptable carrier, and another container (i.e., a second container) comprises an effective amount of another pharmaceutically active ingredient, the combined quantities of the compound of formula (I) and the other pharmaceutically active ingredient being effective to: (a) treat Alzheimer's disease, or (b) inhibit the deposition of amyloid protein in, on or around neurological tissue (e.g., the brain), or (c) treat neurodegenerative diseases, or (d) modulate the activity of gamma-secretase.

This invention also provides a kit comprising, in separate containers, in a single package, pharmaceutical compositions for use in combination, wherein one container comprises an effective amount of a compound of formula (I) in a pharmaceutically acceptable carrier, and another container (i.e., a second container) comprises an effective amount of another pharmaceutically active ingredient (as described below), the combined quantities of the compound of formula (I) and the other pharmaceutically active ingredient being effective to: (a) treat Alzheimer's disease, or (b) inhibit the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain), or (c) treat neurodegenerative diseases, or (d) modulate the activity of gamma-secretase.

This invention also provides any one of the methods disclosed above and below wherein the compound is selected from the group consisting of compounds of the formula: Y1, Y2, Y3, A9-A14, B1-B15, C3-C5, D4, E4, E6-E9, F7-F19, F20d-F20h, F21d-F21h, F22d-F22h, F23c-F23h, F24c-F24h, F25a-F25h, F26a-F26h, F27a-F27h, F28a-F28h, F29a-F29h, F30a-F30h, F31a-F31h, F32a-F32h, F33a-F33h, J1, J2, K7, K8b-K8h, K9a-K9h, K10a-K10h, K11a-K11h, K12a-K12h, K13a-K13h, K14a-K14h, K15a-K15h, K16a-K16h, K17a-K17h, K18a-K18h, K19a-K19h, K20a-K20h, K21a-K21h, K22a-K22h, and X1-X11.

This invention also provides any one of the pharmaceutical compositions disclosed above and below wherein the compound is selected from the group consisting of the compounds of formula: Y1, Y2, Y3, A9-A14, B1-B15, C3-C5, D4, E4, E6-E9, F7-F19, F20d-F20h, F21d-F21h, F22d-F22h, F23c-F23h, F24c-F24h, F25a-F25h, F26a-F26h, F27a-F27h, F28a-F28h, F29a-F29h, F30a-F30h, F31a-F31h, F32a-F32h, F33a-F33h, J1, J2, K7, K8b-K8h, K9a-K9h, K10a-K10h, K11a-K11h, K12a-K12h, K13a-K13h, K14a-K14h, K15a-K15h, K16a-K16h, K17a-K17h, K18a-K18h, K19a-K19h, K20a-K20h, K21a-K21h, K22a-K22h, and X1-X11.

DETAILED DESCRIPTION

In one embodiment, the present invention discloses compounds which are represented by structural Formula (I), or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, wherein the various moieties are described above.

In another embodiment, the present application discloses a compound, or pharmaceutically acceptable salts, solvates, esters or prodrugs of said compound, said compound having the general structure shown in Formula:

wherein:

- either (i) R¹and R²are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (ii) R²and R⁶are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (iii) R⁶and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (iv) R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (v) R³and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (vi) R³and R⁶are joined together to form a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (vii) R¹⁴and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is a bond, —C(O)—, —O—, —N(R⁵)— or —C(R³)(R⁴)—;
- X is —N(R¹⁴)— or —C(R⁶)(R⁷)—;
- each dashed line of

along with its adjoining single bond, together represents an optional double bond with the proviso that only one such double bond is present at any given time, and further such that when the nitrogen of N(R²)(R¹²) is double bonded to the adjacent carbon between said nitrogen and X by the optional double bond, then R¹²is absent;

R¹(when R¹is not joined to R²) is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;

R²(when R²is not joined to R¹, R⁶or R¹⁴) is selected from the group consisting of H, alkyl, alkenyl-, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

R⁵(when R⁵is not joined to R⁶or R¹⁴) is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

R¹²is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

each R¹⁴(when R¹⁴is not joined to R², R³or R⁵) can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

R³(when R³is not joined to R⁶or R¹⁴) is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁴is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁶(when R⁶is not joined to R², R³or R⁵) is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁷is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁸is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, with each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- being unsubstituted or optionally independently substituted with 1-3 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;

R⁹is selected from the group consisting of alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-3 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below,

R¹⁰is selected from the group consisting of a bond, alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl-, heterocyclyalkyl- and the moieties:

where X¹is O, N(R¹⁴) or S;

wherein each of said alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- heterocyclyalkyl- and the above-noted moieties for R¹⁰can be unsubstituted or optionally independently substituted with 1-3 substituents which can be the same or different, each being independently selected from the group consisting of the moieties shown below; and

R¹⁵, R¹⁶and R¹⁷are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, arylheterocyclyl, R¹⁸-alkyl, R¹⁸-cycloalkyl, R¹⁸-cycloalkylalkyl, R¹⁸-heterocyclyl, R¹⁸-heterocyclylalkyl, R¹⁸-aryl, R¹⁸-arylalkyl, R¹⁸-heteroaryl and R¹⁸-heteroarylalkyl;

R¹⁸is 1-5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO₂, halo, heteroaryl, HO-alkyoxyalkyl, —CF₃, —CN, alkyl-CN, —C(O)R¹⁹, —C(O)OH, —C(O)OR¹⁹, —C(O)NHR²⁰, —C(O)NH₂, —C(O)NH₂—C(O)N(alkyl)₂, —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR¹⁹, —S(O)₂R²⁰, —S(O)NH₂, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O)₂NH₂, —S(O)₂NHR¹⁹, —S(O)₂NH(heterocyclyl), —S(O)₂N(alkyl)₂, —S(O)₂N(alkyl)(aryl), —OCF₃, —OH, —OR²⁰, —O-heterocyclyl, —O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH₂, —NHR²⁰, —N(alkyl)₂, —N(arylalkyl)₂, —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R²⁰, —NHC(O)NH₂, —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)₂R²⁰, —NHS(O)₂NH(alkyl), —NHS(O)₂N(alkyl)(alkyl), —N(alkyl)S(O)₂NH(alkyl) and —N(alkyl)S(O)₂N(alkyl)(alkyl);

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R¹and R², R²and R⁶, R⁶and R⁵, R²and R¹⁴, R³and R¹⁴, R¹⁴and R⁵or R³and R⁶, or the 5-14 membered aryl, 5-8 membered cycloalkyl or 5-8 membered cycloalkenyl moiety formed from the joining of R³and R⁶are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵;

wherein each of the alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R²¹are independently unsubstituted or substituted by 1 to 5 R²²groups independently selected from the group consisting of alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, halo, —CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, -alkyl-C(O)OR¹⁵, C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃, ═NOR¹⁵, —NO₂, —S(O)R¹⁵and —S(O)₂R¹⁵.

The statement above: “either (i) R¹and R²are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (ii) R²and R⁶are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (iii) R⁶and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (iv) R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (v) R³and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (vi) R³and R⁶are joined together to form a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or (vii) R¹⁴and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;” means that the occurrences of (i), (ii), (iii), (iv), (v), (vi) and (vii) are mutually exclusive and that only one of (i), (ii), (iii), (iv), (v) (vi) and (vii) can be present at any given time.

It should be understood that when R¹and R²are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

It should be understood that when R²and R⁶are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

It should be understood that when R⁶and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

It should be understood that when R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

It should be understood that when R³and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

It should be understood that when R³and R⁶are joined together to form a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

It should be understood that when R¹⁴and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, each of said heteroaryl, heterocyclyl or heterocyclenyl moiety independently may optionally additionally be fused with an aryl or heteroaryl ring, wherein the ring moiety resulting from the fusion may be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown above.

Thus, in one embodiment, the present application discloses a compound of the Formula (I):

or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, wherein:

either

- (i) R¹and R²are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (d) said heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups; or
- (ii) R²and R⁶are joined together to form a 5-14 membered heteroaryl,

5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (d) said heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups; or

- (iii) R⁵and R⁶are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (d) said heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups; or
- (iv) R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (d) said heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups; or
- (v) R³and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (d) said heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups; or
- (vi) R³and R⁶are joined together to form a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said aryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said cycloalkyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said cycloalkenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (d) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (e) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (f) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (g) said aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups; or
- (vii) R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, wherein: (a) said heteroaryl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (b) said heterocyclyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, (c) said heterocyclenyl moiety is optionally substituted with 1 to 5 independently selected R²¹groups, and (d) said heteroaryl, heterocyclyl or heterocyclenyl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups;

W is —S(O)—, —S(O)₂— or —C(O)—;

U is a bond, —C(O)—, —O—, —N(R⁵)— or —C(R³)(R⁴)—;

X is —N(R¹⁴)— or —C(R⁶)(R⁷)—;

The dashed lines in formula (I) represent optional bonds provided that: (a) only one optional bond can be present (i.e, either there can be an optional bond between X and the adjacent ring carbon, or there can be an optional bond between the nitrogen and the ring carbon), and (b) when the optional bond between the nitrogen (of the NR²moiety) and the ring carbon is present then R¹²is absent (i.e., there is no R¹²moiety bound to the nitrogen);

R¹(when R¹is not joined to R²) is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-, wherein each of said alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-R¹group is optionally substituted with 1-5 independently selected R²¹substituents;

R²(when R²is not joined to R¹, R⁶or R¹⁴) is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶), and wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl-R²group is optionally substituted with 1-5 independently selected R²¹groups;

R³(when R³is not joined to R⁶or R¹⁴) is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-R³group is optionally substituted with 1-5 independently selected R²¹groups;

R⁴is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, and wherein each of said alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-R⁴group is optionally substituted with 1-5 independently selected R²¹substituents;

R⁵(when R⁵is not joined to R⁶or R¹⁴) is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶), and wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl R⁵groups is optionally substituted with 1-5 independently selected R²¹groups;

R⁶(when R⁶is not joined to R², R³or R⁵) is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-R⁶group is optionally substituted with 1-5 independently selected R²¹;

R⁷is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-, and wherein each of said alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-R⁷group is optionally substituted with 1-5 independently selected R²¹substituents;

R⁸is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-, and wherein each of said alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-R⁸group is optionally substituted with 1-3 independently selected R²¹substituents;

R⁹is independently selected from the group consisting of alkyl, alkenyl alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-, and wherein each of said alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclyalkyl-R⁹group is optionally substituted with 1-3 independently selected R²¹groups,

R¹⁰is independently selected from the group consisting of: a bond, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl, heterocyclyalkyl-,

wherein X¹is O, N(R¹⁴) or S; and wherein each of said R¹⁰moieties (except for the bond) is optionally substituted with 1-3 independently selected R²¹substituents;

R¹²is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, —CN, —C(O)R¹⁶, —C(O)OR¹⁶, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶), and wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl-R¹²group is optionally substituted with 1 to 5 independently selected R²¹groups;

R¹⁴(when R¹⁴is not joined to R², R³or R⁵) is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶), and wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl-R¹⁴group is optionally substituted with 1 to 5 independently selected R²¹groups;

R¹⁵, R¹⁶and R¹⁷are each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, arylcycloalkyl-, arylheterocyclyl-, (R¹⁸)_n-alkyl-, (R¹⁸)_n-cycloalkyl-, (R¹⁸)_n-cycloalkylalkyl-, (R¹⁸)_n-heterocyclyl-, (R¹⁸)_n-heterocyclylalkyl-, (R¹⁸)_n-aryl-, (R¹⁸)_n-arylalkyl-, (R¹⁸)_n-heteroaryl- and (R¹⁸)_n-heteroarylalkyl, wherein n is 1 to 5;

Each R¹⁸is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl-, arylalkenyl-, arylalkynyl-, —NO₂, halo, heteroaryl, HO-alkyoxyalkyl-, —CF₃, —CN, -alkyl-CN, —C(O)R¹⁹, —C(O)OH, —C(O)OR¹⁹, —C(O)NHR²⁰, —C(O)NH₂, —C(O)NH₂—C(O)N(alkyl)₂, —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR¹⁹, —S(O)₂R²⁰, —S(O)NH₂, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O)₂NH₂, —S(O)₂NHR¹⁹, —S(O)₂NH(heterocyclyl), —S(O)₂N(alkyl)₂, —S(O)₂N(alkyl)(aryl), —OCF₃, —OH, —OR²⁰, —O-heterocyclyl, —O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH₂, —NHR²⁰, —N(alkyl)₂, —N(arylalkyl)₂, —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R²⁰, —NHC(O)NH₂, —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)₂R²⁰, —NHS(O)₂NH(alkyl), —NHS(O)₂N(alkyl)(alkyl), —N(alkyl)S(O)₂NH(alkyl) and —N(alkyl)S(O)₂N(alkyl)(alkyl);

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is independently selected from the group consisting of: alkyl, cycloalkyl, aryl, arylalkyl- and heteroarylalkyl-;

R²⁰is independently selected from the group consisting of: alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl-, heteroaryl or heteroarylalkyl;

each R²¹is independently selected from the group consisting of: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl-, cycloalkenyl, heterocyclyl, heterocyclylalkyl-, aryl, arylalkyl-, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and wherein each of the alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl R²¹groups is optionally substituted with 1 to 5 independently selected R²²groups (those skilled in the art will appreciate that the optional R²²substitution on one R²¹group is independent of the optional R²²substitution on any other R²¹group, and when there is more than one optional R²²substituent on the same R²¹group each optional R²²substitutent is independently selected);

Each R²²is independently selected from the group consisting of: alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, halo, —CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, -alkyl-C(O)OR¹⁵, C(O)N(R¹⁵)(R¹⁶), —SR'⁵, —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃, ═NOR¹⁵, —NO₂, —S(O)R¹⁵and —S(O)₂R¹⁵.

wherein:

- R¹and R²are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is a bond, —C(O)—, —O—, —N(R⁵)— or —C(R³)(R⁴)—;
- X is —N(R¹⁴)— or —C(R⁶)(R⁷)—;
- each dashed line of

R⁵is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

each R¹⁴can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

R³is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁴is independently selected from the group consisting of H, alkyl-, alkenyl-alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁶is selected from the group consisting of H, alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁷is selected from the group consisting of H, alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁸is selected from the group consisting of H, alkyl-, alkenyl- alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, with each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- being unsubstituted or optionally independently substituted with 1-3 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;

R⁹is selected from the group consisting of alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-3 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below,

R¹⁰is selected from the group consisting of a bond, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl-, heterocyclyalkyl- and the moieties:

where X¹is O, N(R¹⁴) or S;

wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- heterocyclyalkyl- and the above-noted moieties for R¹⁰can be unsubstituted or optionally independently substituted with 1-3 substituents which can be the same or different, each being independently selected from the group consisting of the moieties shown below; and

R¹⁸is 1-5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO₂, halo, heteroaryl, HO-alkyoxyalkyl, —CF₃, —CN, alkyl-CN, —C(O)R¹⁹, —C(O)OR¹⁹, —C(O)NHR²⁰, —C(O)NH₂, —C(O)NH₂—C(O)N(alkyl)₂, —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR¹⁹, —S(O)₂R²⁰, —S(O)NH₂, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O)₂NH₂, —S(O)₂NHR¹⁹, —S(O)₂NH(heterocyclyl), —S(O)₂N(alkyl)₂, —S(O)₂N(alkyl)(aryl), —OCF₃, —OH, —OR²⁰, —O-heterocyclyl, —O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH₂, —NHR²⁰, —N(alkyl)₂, —N(arylalkyl)₂, —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R²⁰, —NHC(O)NH₂, —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)₂R²⁰, —NHS(O)₂NH(alkyl), —NHS(O)₂N(alkyl)(alkyl), —N(alkyl)S(O)₂NH(alkyl) and —N(alkyl)S(O)₂N(alkyl)(alkyl);

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R¹and R²are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵;

wherein:

- R²and R⁶are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is a bond, —C(O)—, —O—, —N(R⁵)— or —C(R³)(R⁴)—;
- X is —C(R⁶)(R⁷)—;
- each dashed line of

R¹is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;

R³is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

where X¹is O, N(R¹⁴) or S;

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R³, R⁴, R⁵, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R²and R⁶are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein each of the alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R²¹are independently unsubstituted or substituted by 1 to 5 R²²groups independently selected from the group consisting of alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, halo, —CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, -alkyl-C(O)OR¹⁵, C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃, ═NOR¹⁵, —NO₂, —S(O)R¹⁵and —S(O)₂R¹⁵.

wherein:

- R⁶and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is —N(R⁵)—;
- X is —C(R⁶)(R⁷)—;
- each dashed line of

R²is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

R¹²is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶)^{, —S}(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

R³is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

where X¹is O, N(R¹⁴) or S;

R¹⁵, R¹⁶and R¹⁷are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, arylheterocyclyl, R¹⁸-alkyl, R¹⁸-cycloalkyl, R¹⁸-cycloalkylalkyl, R¹⁸-heterocyclyl, R¹⁶-heterocyclylalkyl, R¹⁸-aryl, R¹⁸-arylalkyl, R¹⁸-heteroaryl and R¹⁸-heteroarylalkyl;

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R², R³, R⁴, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R⁶and R⁵are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁵, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein:

- R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is a bond, —C(O)—, —O—, —N(R⁵)— or —C(R³)(R⁴)—;
- X is —N(R¹⁴)—;
- each dashed line of

each R¹⁴(when R¹⁴is not joined to R²) can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

R³is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁶is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

where X¹is O, N(R¹⁴) or S;

R¹⁸is 1-5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO₂, halo, heteroaryl, HO-alkyoxyalkyl, —CF₃, —CN, alkyl-CN, —C(O)R¹⁹, —C(O)OH, —C(O)OR¹⁹, —C(O)NHR²⁰, —C(O)NH₂, —C(O)NH₂—C(O)N(alkyl)₂, —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR¹⁹, —S(O)₂R²⁰, —S(O)NH₂, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O)₂NH₂, —S(O)₂NHR¹⁹, —S(O)₂NH(heterocyclyl), —S(O)₂N(alkyl)₂, —S(O)₂N(alkyl)(aryl), —OCF₃, —OH, —OR²⁰, —O-heterocyclyl, —O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH₂, —NHR²⁰, —N(alkyl)₂, —N(arylalkyl)₂, —N(arylalkyl)-(heteroarylalkyl); —NHC(O)R²⁰, —NHC(O)NH₂, —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)₂R²⁰, —NHS(O)₂NH(alkyl), —NHS(O)₂N(alkyl)(alkyl), —N(alkyl)S(O)₂NH(alkyl) and —N(alkyl)S(O)₂N(alkyl)(alkyl);

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R²and R¹⁴are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein:

- R³and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is —C(R³)(R⁴)—;
- X is —N(R¹⁴)—;
- each dashed line of

R¹²is independently selected from the group consisting of H, alkyl, alkenyl; alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

each R¹⁴(when R¹⁴is not joined to R³) can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

R⁶is selected from the group consisting of H, alkyl-, alkenyl- and alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

where X¹is O, N(R¹⁴) or S;

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R², R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R³and R¹⁴are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein each of the alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R²¹are independently unsubstituted or substituted by 1 to 5 R²²groups independently selected from the group consisting of alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, halo, —CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, -alkyl-C(O)OR¹⁵, C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁶)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —N(R¹⁵)S(O)R¹⁶, —N(R¹⁶)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁶)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃, ═NOR¹⁵, —NO₂, —S(O)R¹⁵and —S(O)₂R¹⁵.

wherein:

- R³and R⁶are joined together to form a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is —C(R³)(R⁴)—;
- X is —C(R⁶)(R⁷)—;
- each dashed line of

R²is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶) S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

each R¹⁴can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁶, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

where X¹is O, N(R¹⁴) or S;

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R², R⁴, R⁵, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R³and R⁶are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein:

- R¹⁴and R⁵are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —S(O)—, —S(O)₂— or —C(O)—;
- U is —N(R⁵)—;
- X is —N(R¹⁴)—;
- each dashed line of

R¹²is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁶, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

each R¹⁴(when R¹⁴is not joined to R⁵) can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

R³is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

where X¹is O, N(R¹⁴) or S;

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R¹, R², R³, R⁴, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R¹⁴and R⁵are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR'^s, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein each of the alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R²¹are independently unsubstituted or substituted by 1 to 5 R²²groups independently selected from the group consisting of alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, halo, —CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, -alkyl-C(O)OR¹⁵, C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁵)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃, ═NOR¹⁵, —NO₂, —S(O)R¹⁵and —S(O)₂R¹⁵.

In another embodiment of this invention, R¹and R²are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R¹and R²are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R¹and R²are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention R²and R⁶are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R²and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered aryl moiety.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered aryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered aryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered aryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered aryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered aryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkyl moiety.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkenyl moiety.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered cycloalkenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R³and R⁶are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-14 membered heteroaryl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form 5-8 membered heterocyclyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form 5-8 membered heterocyclenyl moiety substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl or heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with an aryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment of this invention, R⁵and R¹⁴are joined together to form a 5-8 membered heterocyclenyl moiety optionally substituted with 1 to 5 independently selected R²¹groups, and said heteroaryl moiety is optionally fused with a heteroaryl ring, and the ring moiety resulting from the fusion is optionally substituted with 1 to 5 independently selected R²¹groups.

In another embodiment, W is —C(O)—.

In another embodiment, X is —N(R¹⁴)—.

In another embodiment, U is a bond.

In another embodiment, R⁸is H.

In another embodiment, R⁸is alkyl.

In another embodiment, R⁸is methyl.

In another embodiment R¹and R²are joined together to form a moiety selected from the group consisting of:

In another embodiment R²and R¹⁴are joined together to form a moiety selected from the group consisting of:

In another embodiment R³and R¹⁴are joined together to form

In another embodiment, R¹and R²are joined together to form

In another embodiment, R²and R¹⁴are joined together to form

In another embodiment, R¹and R²are joined together to form

In another embodiment, R²and R¹⁴are joined together to form

In another embodiment, R³and R¹⁴are joined together to form

In another embodiment, R²and R¹⁴are joined together to form

In another embodiment, R³and R⁶are joined together to form

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

In another embodiment, R¹and R²are joined together to form

In another embodiment, R⁴is H and R¹and R²are joined together to form

which can, for example, tautomerize to:

Thus another embodiment of this invention is directed to the tautomers of:

said tautomers being selected from the group consisting of:

In another embodiment, R¹⁰is aryl- and said aryl- is unsubstituted.

In another embodiment, R¹⁰is

In another embodiment, R¹⁰is aryl- and said aryl- is substituted with 1-3 substitutents, which can be the same or different, each being independently selected from the group consisting of halo, alkyl, —CN, —NH₂, —NH(alkyl), —N(alkyl)₂, hydroxy and alkoxy groups.

In another embodiment, R¹⁰is

and R¹⁰is substituted with 1-3 substitutents, which can be the same or different, each being independently selected from the group consisting of halo, alkyl, CN, NH₂, NH(alkyl), N(alkyl)₂, hydroxy and alkoxy groups.

In another embodiment R¹⁰is aryl substituted with 1 to 3 independently selected R²¹moieties.

In another embodiment R¹⁰is aryl substituted with 1 to 3 R²¹moieties, wherein each R²¹moiety is the same or different —OR¹⁵group.

In another embodiment R¹⁰is aryl substituted with 1 R²¹moiety.

In another embodiment R¹⁰is aryl substituted with one R²¹moiety, and said R²¹moiety is —OR¹⁵.

In another embodiment R¹⁰is phenyl substituted with 1 to 3 independently selected R²¹moieties.

In another embodiment R¹⁰is phenyl substituted with 1 to 3 R²¹moieties, wherein each R²¹moiety is the same or different —OR¹⁵group.

In another embodiment R¹⁰is phenyl substituted with 1 R²¹moiety.

In another embodiment R¹⁰is phenyl substituted with one R²¹moiety, and said R²¹moiety is —OR¹⁵.

In another embodiment R¹⁰is phenyl substituted with one R²¹moiety, said R²¹moiety is —OR¹⁵, and said R¹⁵is alkyl.

In another embodiment R¹⁰is:

wherein the —R¹⁰-R⁹moiety is:

In another embodiment R¹⁰is aryl substituted with 1 to 3 R²¹moieties, wherein each R²¹moiety is the same or different halo.

In another embodiment R¹⁰is aryl substituted with 1 to 3 R²¹moieties, wherein each R²¹moiety is F.

In another embodiment R¹⁰is aryl substituted with one R²¹moiety, and said R²¹moiety is halo.

In another embodiment R¹⁰is aryl substituted with one R²¹moiety, said R²¹moiety is -halo, and said halo is F.

In another embodiment R¹⁰is phenyl substituted with 1 to 3 R²¹moieties, wherein each R²¹moiety is the same or different halo.

In another embodiment R¹⁰is phenyl substituted with 1 to 3 R²¹moieties, wherein each R²¹moiety is F.

In another embodiment R¹⁰is phenyl substituted with one R²¹moiety, and said R²¹moiety is halo.

In another embodiment R¹⁰is phenyl substituted with one R²¹moiety, said R²¹moiety is -halo, and said halo is F.

In another embodiment R¹⁰is:

wherein the —R¹⁰-R⁹moiety is:

In another embodiment R¹⁰is selected from the group consisting of:

In another embodiment, R¹⁰is unsubstituted heteroaryl.

In another embodiment, R¹⁰is heteroaryl substituted with 1-3 substitutents, which can be the same or different, each being independently selected from the group consisting of halo, alkyl, CN, NH₂, NH(alkyl), N(alkyl)₂, hydroxy and alkoxy groups.

In another embodiment R¹⁰is unsubstituted heteroaryl wherein said heteroaryl is pyridyl.

In another embodiment R¹⁰is:

wherein the —R¹⁰-R⁹moiety is:

In another embodiment, R¹⁰is aryl- and said aryl- is substituted with 1-3 substitutents, which can be the same or different, each being an alkoxy group.

In another embodiment, R¹⁰is

and R¹⁰is substituted with 1-3 substitutents, which can be the same or different, each being an alkoxy group.

In another embodiment, R¹⁰is aryl- is substituted with methoxy.

In another embodiment, R¹⁰is

In another embodiment, R⁹is unsubstituted heteroaryl.

In another embodiment of this invention R⁹is selected from the group consisting of heteroaryl and heteroaryl substituted with 1-3 R²¹groups, and wherein each R²¹is independently selected.

In another embodiment, R⁹is heteroaryl which is substituted with 1-3 substituents which can be the same or different, each substituent being independently selected from the group consisting of halo, alkyl, CN, NH₂, NH(alkyl), N(alkyl)₂, hydroxyl, alkoxy, alkyl substituted with halo (e.g., alkyl substituted with F, such as, for example, —CH₂F), and alkyl substituted with —OR¹⁵(such as, for example, alkyl substituted with —OR¹⁵wherein R¹⁵is H, that is, —CH₂OH).

In another embodiment of this invention R⁹is selected from the group consisting of imidazolyl and imidazolyl substituted with 1-3 R²¹groups, and wherein each R²¹is independently selected.

In another embodiment of this invention R⁹is imidazolyl substituted with 1-3 R²¹groups, and wherein each R²¹is independently selected.

In another embodiment, R⁹is imidazolyl which is substituted with 1-3 substituents which can be the same or different, each substituent being independently selected from the group consisting of halo, alkyl, CN, NH₂, NH(alkyl), N(alkyl)₂, hydroxyl, alkoxy, alkyl substituted with halo (e.g., alkyl substituted with F, such as, for example, —CH₂F), and alkyl substituted with —OR¹⁵(such as, for example, alkyl substituted with —OR¹⁵wherein R¹⁵is H, that is, —CH₂OH).

In another embodiment, R⁹is imidazolyl substituted with 1-3 substituents independently selected from the group consisting of halo, alkyl, CN, NH₂, NH(alkyl), N(alkyl)₂, hydroxy and alkoxy groups.

In another embodiment, R⁹is imidazol-1-yl.

In another embodiment, R⁹is 4-methyl-imidazol-1-yl.

In another embodiment, R⁹is:

In another embodiment R¹⁰is selected from the group consisting of aryl and aryl substituted with one or more R²¹groups, and R⁹is selected from the group consisting of heteroaryl and heteroaryl substituted with one or more R²¹groups, and wherein each R²¹is independently selected.

In another embodiment R¹⁰is selected from the group consisting of phenyl and phenyl substituted with 1-3 independently selected R²¹groups, and R⁹is selected from the group consisting of imidazolyl and imidazolyl substituted with 1-3 independently selected R²¹groups.

In another embodiment R¹⁰is phenyl substituted with 1-3 independently selected R²¹groups, and R⁹is selected from the group consisting of imidazolyl and imidazolyl substituted with 1-3 independently selected R²¹groups.

In another embodiment R¹⁰is selected from the group consisting of heteroaryl and heteroaryl substituted with 1-3 R²¹groups, and the R⁹group is selected from the group consisting of heteroaryl and heteroaryl substituted with 1-3 R²¹groups, and wherein each R²¹is independently selected.

In another embodiment R¹⁰is selected from the group consisting of pyridyl and pyridyl substituted with 1-3 R²¹groups, and the R⁹group is selected from the group consisting of imidazolyl and imidazolyl substituted with 1-3 R²¹groups, and wherein each R²¹is independently selected.

In another embodiment R¹⁰is pyridyl, and the R⁹group is imidazolyl substituted with 1-3 R²¹groups, and wherein each R²¹is independently selected.

In another embodiment the R⁹-R¹⁰— moiety is:

In another embodiment R⁹-R¹⁰— moiety is:

In another embodiment, R²¹is independently selected from the group consisting of alkyl, alkyl-OH, unsubstituted arylalkyl-, arylalkyl wherein said aryl-portion of arylalkyl- is substituted with 1-3 halogen, unsubstituted aryl- and aryl wherein said aryl- is substituted with 1-3 halogen.

In another embodiment, R²¹is independently selected from the group consisting of alkyl, alkyl-OH,

In another embodiment, R³, R⁴, R⁶and R⁷can be the same or different, each being independently selected from the group consisting of H and alkyl.

In another embodiment, R³, R⁴, R⁶and R⁷can be the same or different, each being independently selected from the group consisting of H and methyl.

In another embodiment R²¹is alkyl.

In another embodiment R²¹is -alkyl-OH.

In another embodiment R²¹is

wherein:

W is —C(O)—;

U is a bond or —C(R³)(R⁴)—;

X is —N(R¹⁴)—;

each dashed line of

R¹and R²are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 R²¹groups which can be the same or different;

R²¹is independently selected from the group consisting of alkyl, alkyl-OH,

R⁹is H or alkyl;

R¹⁰is

and

R⁹is 4-methyl-imidazol-1-yl.

wherein:

W is —C(O)—;

U is a bond or —C(R³)(R⁴)—;

X is —N(R¹⁴)—;

each dashed line of

R¹is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-being unsubstituted or optionally independently being substituted with 1-5 R²¹groups which can be the same or different;

R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 R²¹groups which can be the same or different;

each R¹⁴(when not joined to R²) can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl;

. R²¹is independently selected from the group consisting of alkyl, alkyl-OH,

R⁸is H or alkyl;

R¹⁰is

and

R⁹is 4-methyl-imidazol-1-yl.

wherein:

- R²and R⁶are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below; or R²and R¹⁴are joined together to form a 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of the moieties shown below;
- W is —C(O)—;
- U is a bond or —C(R³)(R⁴)—;
- X is —C(R⁶)(R⁷)—;
- each dashed line of

R¹is independently selected from the group consisting of: alkyl, alkyl-OH,

R¹²is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶)_n—S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶and —P(O)(OR¹⁵)(OR¹⁶);

each R¹⁴(when R¹⁴is not connected to R²) can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁶, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —S(O)R¹⁵, —S(O)₂R¹⁵, —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶);

R³is independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁶(when R⁶is not connected to R²) is selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each of said alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionally independently substituted with 1-5 substituents which can be the same or different, each substituent being independently selected from the group consisting of consisting of the moieties shown below;

R⁸is H or alkyl;

R¹⁰is

R⁹is 4-methyl-imidazol-1-yl;

or, alternately, two R¹⁸moieties on adjacent carbons can be linked together to form:

R¹⁹is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R²⁰is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R³, R⁴, R⁵, R⁶, R⁷, R¹²and R¹⁴, the 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety formed from the joining of R²and R¹⁴or R²and R⁶are independently unsubstituted or substituted by 1 to 5 R²¹groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶), —N(R¹⁵)S(O)R¹⁶, —N(R¹⁵)S(O)₂R¹⁶, —CH₂—N(R¹⁵)S(O)₂R¹⁶, —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —S(O)R¹⁵, ═NOR¹⁵, —N₃, —NO₂and —S(O)₂R¹⁵; and

wherein:

W is —C(O)—;

U is —C(R³)(R⁴)—;

X is —C(R⁶)(R⁷)—;

each dashed line of

R¹is independently selected from the group consisting of H, methyl,

R³and R⁶are joined together to form a 5-14 membered aryl, 5-8 membered cycloalkyl, 5-8 membered cycloalkenyl, 5-14 membered heteroaryl, 5-8 membered heterocyclyl or 5-8 membered heterocyclenyl moiety, with each of said aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl or heterocyclenyl moiety being unsubstituted or optionally independently being substituted with 1-5 R²¹groups which can be the same or different;

R²¹is independently selected from the group consisting of alkyl, alkyl-OH,

R⁸is H or alkyl;

R¹⁰is

and

R⁹is 4-methyl-imidazol-1-yl.

Another embodiment is directed to compounds of formula (I) wherein:

- W is —C(O)—;
- U is —C(R³)(R⁴)—;
- X is —N(R¹⁴)—;
- R¹is alkyl, alkyl-OH,

- R²¹is independently selected from the group consisting of alkyl, alkyl-OH,

- R⁸is H or alkyl;
- R¹⁰is

- and
- R⁹is 4-methyl-imidazol-1-yl.

Another embodiment of this invention is directed to compounds of formula (I) wherein: (a) R¹and R²are joined together to form a 5-14 membered heteroaryl moiety, (b) W is —C(O)—, (c) U is a bond or —C(R³)(R⁴)—, (d) X is —N(R¹⁴)—, (e) R⁸is H or alkyl, (f) R¹⁰is