PYRAZOLE DERIVATIVES AS TNIK, IKKe AND TBK1 INHIBITOR AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

摘要

Provided is pyrazole derivatives as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the pyrazole derivative according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.

主权项

1. A compound selected from the group consisting of a pyrazole derivative of formula (I) and a pharmaceutically acceptable salt, a hydrate, and a solvate thereof: wherein: A is benzene or thiophene ring; X is —NH—C(═O) or —NH—S(═O)2—; m is 0 or 1; R1 is substituted or unsubstituted C5-14 aryl or substituted or unsubstituted 5- to 13-membered heteroaryl; said aryl is optionally substituted with one or more substituents selected from the group consisting of hydroxy; halogen; C1-7 alkyl; C1-7 alkoxy; C1-7 alkylthio; 5- to 10-membered heterocycloalkyl which is optionally substituted with one or more substituents selected from hydroxy, C1-7 alkyl, C1-7 alkoxy, t-butyloxycarbonyl or C1-7 alkyl-carbonyl; nitro; amino; 5- to 13-membered heteroaryl; (diC1-7 alkyl)amino; —NH—(CH2)p—R3; —O—(CH2)p—R3; and —NH—C(═O)—R3; R3 being H, hydroxy, C1-7 alkoxy, 5- to 10-membered heterocycloalkyl which is unsubstituted or substituted with at least one alkyl, (diC1-7 alkyl)amino, C1-7 alkylamino, C1-7 alkyl, saturated or unsaturated C3-10 cycloalkyl, (trifluoromethyl) (saturated or unsaturated C3-10 cycloalkyl), 5- to 13-membered heteroaryl or oxo-C3-10 cycloalkyl; and p being an integer from 0 to 7; Y isR4 and R5 being each independently hydrogen, C1-7 alkyl, C3-10 cycloalkyl, hydroxy-C1-7 alkyl or —CF3; R6 being hydrogen or C1-7 alkyl; R7 being 5- to 13-membered heteroaryl; and R4 and R5 being optionally bonded to each other to form C3-10 cycloalkyl;
n is 0 or 1; and R2 is hydroxy, C1-7 alkyl, cyano, hydroxy-C1-7 alkyl, substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted C5-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl; said cycloalkyl, aryl, heteroaryl or heterocycloalkyl being optionally substituted with one or more substituents selected from the group consisting of halogen, C1-7 alkyl and —(CH2)q-(5- to 10-membered heterocycloalkyl); and q being an integer from 0 to 2.