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US 2016/0108061 A1Published application
Acc inhibitors and uses thereof
AssigneeNimbus Apollo, Inc.
InventorsJeremy Robert Greenwood, Geraldine C. Harriman, George Borg, Craig E. Masse
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Abstract
The present invention provides compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same. Specifically, bicyclic heteroaryl derivatives containing a imidazole, thiazole or oxazole fused to a pyridinone, pyrimidinone or pyrimidindione are provided. These compounds have therapeutic utility toward treating an ACC enzyme mediated disorder such as obesity in a subject, upon administration in an effective amount to said subject.
Claims14
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- W is oxygen or sulfur;
- Q is C or N;
- wherein if Q is N, then Rz is absent;
- X is —O—, —S—, or —NR—;
- each Z is independently C or N;
- provided that both Z are not N;
- R1 is hydrogen or C1-4 aliphatic, optionally substituted with one or more halogens, —OR, —SR, —N(R)2, —N(R)C(O)R, —C(O)N(R)2, —N(R)C(O)N(R)2, —N(R)C(O)OR, —OC(O)N(R)2, —N(R)SO2R, —SO2RN(R)2, —C(O)R, —C(O)OR, —OC(O)R, —C(O)OR, —S(O)R, or —SO2R;
- R2 is halogen, —R, —OR, —SR, —N(R)2, —N(R)C(O)R, —C(O)N(R)2, —N(R)C(O)N(R)2, —N(R)C(O)OR, —OC(O)N(R)2, —N(R)SO2R, —SO2N(R)2, —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, —SO2R, —B(OR)2, or Hy, where Hy is selected from 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- or
- R1 and R2 are taken together to form an optionally substituted 4-7 membered partially unsaturated carbocyclo-, or heterocyclo-, benzo-, or 5-6 membered heteroarylo-fused ring;
- each R is independently hydrogen, deuterium, or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring;
- a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- L1 is a covalent bond or a 1-6 membered straight or branched bivalent hydrocarbon chain optionally substituted with R5 and R5′;
- L2 is a covalent bond or a 1-6 membered straight or branched bivalent hydrocarbon chain optionally substituted with R7 and R7′;
- R3 is halogen, —CN, —OR, —SR, —N(R)2, —N(R)C(O)R, —C(O)RN(R)2, —C(O)N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(O)OR, —OC(O)N(R)2, —N(R)SO2R, —SO2N(R)2, —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, —SO2R, —B(OR)2, or an optionally substituted ring selected from phenyl or 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- R4 is hydrogen or a ring selected from a 3-8 membered monocyclic saturated or partially unsaturated carbocyclic ring, a 4-8 membered monocyclic saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, an 8-10 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- wherein said ring is optionally substituted with n instances of R8;
- each of R5 and R5′ is independently —R, —OR, —SR, —N(R)2, —N(R)C(O)R, —C(O)N(R)2, —N(R)C(O)N(R)2, —N(R)C(O)OR, —OC(O)N(R)2, —N(R)SO2R, —SO2N(R)2, —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, or —SO2R;
- or R5 and R5′ are taken together to form a cyclopropylenyl, cyclobutylenyl, or oxetanyl group;
- and
- each of R7 and R7′ is independently, —R, —OR6, —SR, —N(R)2, —N(R)C(O)R, —C(O)N(R)2, —N(R)C(O)N(R)2, —N(R)C(O)OR, —OC(O)N(R)2, —N(R)SO2R, —SO2N(R)2, —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, —SO2R, —B(OR)2;
- or R7 and R7′ are taken together to form a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- R6 is —R, —C(O)N(R)2, or —C(O)R;
- each R8 is independently selected from halogen, —R, —OR, —SR, —N(R)2 or deuterium;
- Rz is selected from hydrogen, halogen, methyl, —CN, ═O, and ═S;
- and
- n is 0-5.
25 more elements
Dependencies are inferred from the claim text.