Discovery of 1 H -pyrazol-3(2 H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK)

Journal of Medicinal Chemistry

Volumn 58, Issue 3, 2015, Pages 1426-1441

  Smith, Adrian L ^a   Andrews, Kristin L ^b   Beckmann, Holger ^e   Bellon, Steven F ^b   Beltran, Pedro J ^c   Booker, Shon ^a   Chen, Hao ^d   Chung, Young Ah ^c   D'Angelo, Noel D ^a   Dao, Jennifer ^b   Dellamaggiore, Kenneth R ^c   Jaeckel, Peter ^e   Kendall, Richard ^c   Labitzke, Katja ^e   Long, Alexander M ^b   Materna Reichelt, Silvia ^e   Mitchell, Petia ^c   Norman, Mark H ^a   Powers, David ^b   Rose, Mark ^d   Shaffer, Paul L ^b   Wu, Michelle M ^c   Lipford, J Russell ^c   more..

^a Departments of Medicinal Chemistry   (United States)

^b Departments of Molecular Structure and Characterization   (United States)

^c Departments of Oncology Research   (United States)

^d AMGEN INC   (United States)

^e Amgen Research GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1 [5 (4 AMINO 7 METHYL 7H PYRROLO[2,3 D]PYRIMIDIN 5 YL) INDOLIN 1 YL) 2 (3 FLUORO 5 (TRIFLUOROMETHYL)PHENYL]ETHANONE; 2 (DIFLUOROMETHYL) 6 (4,4,5,5 TETRAMETHYL 1,3,2 DIOXABOROLAN 2 YL)BENZO[D]THIAZOLE; 2 (FLUOROMETHYL) 6 (4,4,5,5 TETRAMETHYL 1,3,2 DIOXABOROLAN 2 YL)BENZO[D]THIAZOLE; 2 AMINO 3 IODO N (4 METHOXY 3 (TRIFLUOROMETHYL)PHENYL) 4 METHYLBENZAMIDE; 2 AMINO N (4 METHOXY 3 (TRIFLUOROMETHYL)PHENYL) 4 METHYL 3 (2 (METHYLAMINO)QUINAZOLIN 6 YL)BENZAMIDE; 4 (2 AMINO 3 IODO 4 METHYLBENZOYL) 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 4 (3 BROMO 4 CHLOROBENZOYL) 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 4 (3 BROMO 4 METHYLBENZOYL) 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 4 (3 BROMO 4 NITROBENZOYL) 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 4 (3 IODO 4 METHYL 2 NITROBENZOYL) 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 4 (4 AMINO 3 BROMOBENZOYL) 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 4 [2 AMINO 4 METHYL 3 (2 (METHYLAMINO)QUINAZOLIN 6 YL) BENZOYL] 1 METHYL 2,5 DIPHENYL 1H PYRAZOL 3(2H) ONE; 5 CHLORO N METHYL 6 (4,4,5,5 TETRAMETHYL 1,3,2 DIOXABOROLAN 2 YL)QUINAZOLIN 2 AMINE; 5 FLUORO N METHYL 6 (4,4,5,5 TETRAMETHYL 1,3,2 DIOXABOROLAN 2 YL)QUINAZOLIN 2 AMINE; 6 (4,4,5,5 TETRAMETHYL 1,3,2 DIOXABOROLAN 2 YL) 2 (TRIFLUOROMETHYL)BENZO[D]THIAZOLE; 6 BROMO 2 (DIFLUOROMETHYL)BENZO[D]THIAZOLE; 6 BROMO 2 (FLUOROMETHYL)BENZO[D]THIAZOLE; 6 BROMO 2 (TRIFLUOROMETHYL)BENZO[D]THIAZOLE; 6 BROMO 2 METHYLQUINAZOLINE; 6 BROMO 2,5 DICHLOROQUINAZOLINE; 6 BROMO 5 CHLORO N METHYLQUINAZOLIN 2 AMINE; 6 BROMO 5 CHLOROQUINAZOLIN 2 AMINE; 6 BROMO 5 FLUORO N METHYLQUINAZOLIN 2 AMINE; N [5 [(6,7 DIMETHOXYQUINOLIN 4 YL)OXY]PYRIDIN 2 YL] 1 METHYL 3 OXO 2 PHENYL 5 (PYRIDIN 4 YL) 2,3 DIHYDRO 1H PYRAZOLE 4 CARBOXAMIDE; N [5 [(6,7 DIMETHOXYQUINOLIN 4 YL)OXY]PYRIDIN 2 YL] 1 METHYL 3 OXO 2,5 DIPHENYL 2,3 DIHYDRO 1H PYRAZOLE 4 CARBOXAMIDE; PROTEIN KINASE INHIBITOR; PROTEIN KINASE R; PROTEIN KINASE R LIKE ENDOPLASMIC RETICULUM KINASE; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; EIF2AK3 PROTEIN, HUMAN;

ACYLATION; ANIMAL EXPERIMENT; ARTICLE; AUTOPHOSPHORYLATION; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DEAMINATION; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG SYNTHESIS; ENZYME ASSAY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLUORINE NUCLEAR MAGNETIC RESONANCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROGEN BOND; KWASHIORKOR; MALE; MOUSE; NONHUMAN; PROTEIN SYNTHESIS; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; SANDMEYER REACTION; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG DEVELOPMENT; HUMAN; METABOLISM; NUDE MOUSE; SYNTHESIS;

ANIMALS; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; EIF-2 KINASE; HUMANS; MICE; MICE, NUDE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84922778869     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5017494     Document Type: Article

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