Discovery and evaluation of 7- lkyl-1,5-bis-aryl-pyrazolopyridinones as Highly potent, selective, and orally efficacious inhibitors of p38α mitogen-activated protein kinase

Journal of Medicinal Chemistry

Volumn 53, Issue 7, 2010, Pages 2973-2985

  Pettus, Liping H ^a   Wurz, Ryan P ^a   Xu, Shimin ^a   Herberich, Brad ^a   Henkle, Bradley ^a   Liu, Qiurong ^a   McBride, Helen J ^a   Mu, Sharon ^a   Plant, Matthew H ^a   Saris, Christiaan J M ^a   Sherman, Lisa ^a   Wong, Lu Min ^a   Chmait, Samer ^a   Lee, Matthew R ^a   Mohr, Christopher ^a   Hsieh, Faye ^a   Tasker, Andrew S ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2,6 DIFLUOROPHENYL) 7 METHYL 5 [6 METHYL 3 (METHYLAMINO) BENZO [D] ISOXAZOL 7 YL] 1H PYRAZOLO [3,4 B] PYRIDIN 6(7H) ONE DERIVATIVE; 3 [1 (2 CHLOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] N CYCLOPROPYL 4 METHYLBENZAMIDE; 3 [1 (2,6 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL N (ISOXAZOL 3 YL] 4 METHYLBENZAMIDE; 3 [1 (2,6 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] 4 METHYL N (1 METHYLCYCLOPROPYL)BENZAMIDE; 3 [1 (2,6 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] 4 METHYLBENZAMIDE; 4 CHLORO N CYCLOPROPYL 3 [1 (2,6 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] BENZAMIDE; 7 ALKYL 1,5 BIS ARYL PYRAZOLOPYRIDINONE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; N CYCLOPROPYL 3 [1 (2 FLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] 4 METHYLBENZAMIDE; N CYCLOPROPYL 3 [1 (2,4 DIFLUOROPHENYL) 7 ETHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4-B] PYRIDIN 5 YL] 4 METHYLBENZAMIDE; N CYCLOPROPYL 3 [1 (2,4 DIFLUOROPHENYL)7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] 4 METHYLBENZAMIDE; N CYCLOPROPYL 3 [1 (2,5 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO[3,4 B] PYRIDIN 5 YL] 4 METHYLBENZAMIDE; N CYCLOPROPYL 3 [1 (2,6 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL) 4 METHYLBENZAMIDE; N CYCLOPROPYL 3 [1 (2,6 DIFLUOROPHENYL) 7 METHYL 6 OXO 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] 5 FLUORO 4 METHYLBENZAMIDE; N CYCLOPROPYL 4 METHYL 3 (7 METHYL 6 OXO 1 2 TOLYL 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL) BENZAMIDE; N CYCLOPROPYL 4 METHYL 3 [7 METHYL 6 OXO 1 (3 (TRIFLUOROMETHYL) PYRIDIN 2 YL) 6,7 DIHYDRO 1H PYRAZOLO [3,4 B] PYRIDIN 5 YL] BENZAMIDE; PYRIDONE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTHRITIS; ARTICLE; CELL ASSAY; CONTROLLED STUDY; DOSE RESPONSE; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG SCREENING; HUMAN; HUMAN CELL; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; ARTHRITIS; COLLAGEN; DRUG DISCOVERY; HUMANS; MALE; MITOGEN-ACTIVATED PROTEIN KINASE 14; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PROTEIN KINASE INHIBITORS; PYRIDONES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 77950552502     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100095x     Document Type: Article

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