| 摘要 |
587004 Disclosed are isoquinolin-1(2H)-one, naphthyridin-5(6H)-one, 3,4-dihydroisoquinolin-1(2H)-one and analogues thereof as represented by the general formula (I), or a pharmaceutically acceptable salt thereof, wherein Wa1 is CR3 or N; Wa2 is CR5 or N; Wa3 is CR6 or N; Wa4 is CR7 or N; Wb5 is CR8 or CHR8, wherein no more than two adjacent ring atoms selected from Wa1, Wa2, Wa3, Wa4, and Wb5 are heteroatoms; Wd is a heteroaryl selected from the group consisting of: 6-amino-9H-purin-9-yl, 4-amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl, or 4-amino-1H-pyrazolo[4,3-c]pyridin-1-yl, wherein the heteroaryl is optionally substituted; B is alkyl, amino, heteroalkyl, cycloalkyl, heterocycloalkyl, or an optionally substituted monocyclic aryl, heteroaryl, heterocycloalkyl, or cycloalkyl ring system, X is absent or is -(CH(R9))z-; Y is absent, -O-, -S-, -S(=O)-, -S(=O)2-, -N(R9)-, -C(=O)-, -N(R9)-C(=O)-, or -N(R9)-C(=O)NH-,-N(R9)C(R9)2-, or -C(=O)-(CHR9)z-; and wherein the remaining substituents are as defined herein. Representative compounds include 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one, 3-((6-amino-9H-purin-9-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one, 7-((4-amino-3-(3-hydroxyphenyl)- 1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-methyl-6-o-tolyl-1,6-naphthyridin-5(6H)-one and 3-((4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolyl-3,4-dihydroisoquinolin-1(2H)-one. Further disclosed is a composition comprising a pharmaceutically acceptable excipient and a compound as defined above, for use in treating of a disorder chosen from one or more of cancer, bone disorder, inflammatory disease, immune disease, nervous system disease, metabolic disease, respiratory disease, thrombosis, or cardiac disease, including inflammatory or an autoimmune disease, a respiratory disease, asthma, emphysema, allergy, dermatitis, rheumatoid arthritis, osteoarthritis, inflammatory bowel diseases, chronic obstructive pulmonary disorder, psoriasis, multiple sclerosis, disorders related to diabetic complications, lupus erythematosus, scleroderma, graft versus host disease, etc.. |
