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US 10,292,987 B2Granted
Heterocyclic amides as kinase inhibitors
AssigneeGlaxoSmithKline Intellectual Property Development Limited
InventorsJae U. Jeong, Deepak Bandyopadhyay, Patrick M. Eidam, Philip Anthony Harris, Jianxing Kang, Bryan Wayne King, Ami Lakdawala Shah, Lara Kathryn Leister, Attiq Rahman, Joshi M. Ramanjulu, Clark A. Sehon, Robert Singhaus, Jr., Daohua Zhang
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Abstract
Disclosed are compounds having the formula: wherein X, Y, Z1, Z2, Z3, Z4, R5, RA, m, A. L, and B are as defined herein, and methods of making and using the same.
Claims10
A compound according to Formula (I):
- wherein:
- X is O;
- Y is CH2 or CH2CH2;
- Z1 is N, CH or CR1;
- Z2 is CH or CR2;
- Z3 is N, CH or CR3;
- Z4 is CH or CR4;
- R1 is fluoro or methyl;
- one of R2 and R3 is halogen, cyano, (C1-C6)alkyl, halo(C1-C4)alkyl, (C1-C6)alkoxy, halo(C1-C4)alkoxy, hydroxyl, B(OH)2, —COOH, halo(C1-C4)alkylC(OH)2—, (C1-C4)alkoxy(C1-C4)alkoxy, (C1-C4)alkylSO2—, (C1-C4)alkylSO2NHC(O)—, (C1-C4)alkylC(O)NH—, ((C1-C4)alkyl)((C1-C4)alkyl)NC(O)—, (C1-C4)alkylOC(O)—, (C1-C4)alkylC(O)N(C1-C4)alkyl)-, (C1-C4)alkylNHC(O)—, (C1-C4)alkoxy(C2-C4)alkylNHC(O)—, (C1-C4)alkoxy(C2-C4)alkylNHC(O)NH—, (C1-C4)alkylSO2(C2-C4)alkylNHC(O)—,(C1-C4)alkylNHC(O)NH—, (C1-C4)alkylOC(O)NH—, hydroxy(C1-C4)alkylOC(O)NH—, 5-6 membered heterocycloalkyl-C(O)—, 5-6 membered heterocycloalkyl-(C1-C4)alkyl-NHC(O)—, 5-6 membered heterocycloalkyl-(C1-C4)alkoxy-, 3-6 membered cycloalkyl, 5-6 membered heteroaryl, or 5-6 membered heteroaryl-C(O)NH,
- wherein said 3-6 membered cycloalkyl, 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl are optionally substituted by 1 or 2 substituents each independently selected from the group consisting of (C1-C4)alkyl and —(C1-C4)alkyl-CN;
- and the other of R2 and R3 is halogen, cyano or (C1-C6)alkyl;
- R4 is fluoro, chloro, methyl trifluoromethyl;
- R5 is H or methyl,
- A is phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocycloalkyl, wherein the carbonyl moiety and L are substituted 1,3 on ring A;
- m is 0 or m is 1 and RA is (C1-C4)alkyl;
- and
- L is O, S, NH, N(CH3), CH2, CH2CH2, CH(CH3), CHF, CF2, CH2O, CH2N(CH3), CH2NH, or CH(OH);
- B is an optionally substituted (C1-C6)cycloalkyl, phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocycloalkyl;
- wherein said (C3-C6)cycloalkyl, phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocycloalkyl is unsubstituted or is substituted by one or two substituents each independently selected from halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, nitro, and (C1-C4)alkylC(O)—;
- or the moiety -L-B is (C3-C6)alkyl, (C3-C6)alkoxy, halo(C3-C6)alkoxy, (C3-C6)alkenyl, or (C3-C6)alkenyloxy;
- or a pharmaceutically acceptable salt thereof.
18 more elements
Dependencies are inferred from the claim text.