Discovery of AMG 925, a FLT3 and CDK4 dual kinase inhibitor with preferential affinity for the activated state of FLT3

Journal of Medicinal Chemistry

Volumn 57, Issue 8, 2014, Pages 3430-3449

  Li, Zhihong ^a   Wang, Xianghong ^a   Eksterowicz, John ^a   Gribble, Michael W ^a   Alba, Grace Q ^a   Ayres, Merrill ^a   Carlson, Timothy J ^a   Chen, Ada ^a   Chen, Xiaoqi ^a   Cho, Robert ^a   Connors, Richard V ^a   Degraffenreid, Michael ^a   Deignan, Jeffrey T ^a   Duquette, Jason ^a   Fan, Pingchen ^a   Fisher, Benjamin ^a   Fu, Jiasheng ^a   Huard, Justin N ^b   Kaizerman, Jacob ^a   Keegan, Kathleen S ^b   Li, Cong ^a   Li, Kexue ^a   Li, Yunxiao ^a   Liang, Lingming ^a   Liu, Wen ^a   Lively, Sarah E ^a   Lo, Mei Chu ^a   Ma, Ji ^a   McMinn, Dustin L ^a   Mihalic, Jeffrey T ^a   Modi, Kriti ^a   Ngo, Rachel ^a   Pattabiraman, Kanaka ^a   Piper, Derek E ^a   Queva, Christophe ^b   Ragains, Mark L ^a   Suchomel, Julia ^a   Thibault, Steve ^a   Walker, Nigel ^a   Wang, Xiaodong ^a   Wang, Zhulun ^a   Wanska, Malgorzata ^a   Wehn, Paul M ^a   Weidner, Margaret F ^b   Zhang, Alex J ^a   Zhao, Xiaoning ^a   Kamb, Alexander ^a   Wickramasinghe, Dineli ^a   Dai, Kang ^a   McGee, Lawrence R ^a   Medina, Julio C ^a   more..

^a AMGEN INC   (United States)

^b AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [METHYL[1 [6 [[9 [(1,4) 4 METHYLCYCLOHEXYL] 9H PYRIDO [4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 YL]AMINO]PYRIDAZIN 3 YL] PIPERIDIN 4 YL]AMINO]PROPAN 2 OL; 2 AMINO 9 CYCLOPENTYL 7,9 DIHYDRO 8H PYRIDO[4',3':4,5]PYRROLO [2,3 D]PYRIMIDIN 8 ONE; 2 HYDROXY 1 [2 [[9 [(1,4) 4 METHYLCYCLOHEXYL] 9H PYRIDO [4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 YL]AMINO] 7,8 DIHYDRO 1,6 NAPHTHYRIDIN 6(5H) YL]ETHANONE; 2 HYDROXY 1 [4 [6 [[9 ((1,4) 4 METHYLCYCLOHEXYL) 9H PYRIDO [4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 YL]AMINO]PYRIDAZIN 3 YL] PIPERIDIN 1 YL]AMINO]ETHANONE; 5 (3 CHLOROPYRIDIN 4 YL) N4 CYCLOPENTYLPYRIMIDINE 2,4 DIAMINE; 5 BROMO 2 CHLORO N CYCLOPENTYLPYRIMIDIN 4 AMINE; 5 BROMO N4 CYCLOPENTYLPYRIMIDINE 2,4 DIAMINE; 8 CHLORO 9 CYCLOPENTYL 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 8 CHLORO 9 CYCLOPENTYL N [5 (1 PIPERAZINYL) 2 PYRIDINYL] 9H PYRIDO[4',3':4,5] PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 8 [2 METHOXY 6 [[9 [(1,4) 4 METHYLCYCLOHEXYL] 9H PYRIDO[4',3':4,5]PYRROLO [2,3 D]PYRIMIDIN 2 YL]AMINO]PYRIDIN 3 YL] 1,8 DIAZASPIRO[4.5]DECAN 2 ONE; 8 [6 [[9 ((1,4) 4 METHYLCYCLOHEXYL) 9H PYRIDO[4',3':4,5]PYRROLO [2,3 D]PYRIMIDIN 2 YL]AMINO]PYRIDAZIN 3 YL] 2 THIA 8 AZASPIRO[4.5] DECANE 2,2 DIOXIDE; 8 [6 [[9 ((1,4) 4 METHYLCYCLOHEXYL) 9H PYRIDO[4',3':4,5]PYRROLO [2,3 D]PYRIMIDIN 2 YL]AMINO]PYRIDIN 3 YL] 1,8 DIAZASPIRO[4.5]DECAN 2 ONE; 9 CYCLOPENTYL 8 FLUORO 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 9 CYCLOPENTYL 8 METHOXY 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 9 CYCLOPENTYL 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 9 CYCLOPENTYL N [5 (1 PIPERAZINYL) 2 PYRIDINYL] 9H PYRIDO [4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 9 [(1,4) 4 METHYLCYCLOHEXYL]N [6 [4 [(METHYLSULFONYL)METHYL]PIPERIDIN 1 YL]PYRIDAZIN 3 YL] 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D] PYRIMIDIN 2 AMINE; AMG 925; CYCLIN DEPENDENT KINASE 4; FLT3 LIGAND; N [5 [4 (DIMETHYLAMINO)PIPERIDIN 1 YL]6 FLUOROPYRIDIN 2 YL] 9 [(1,4) 4 METHYLCYCLOHEXYL] 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; N [5 [4 (DIMETHYLAMINO)PIPERIDIN 1 YL]6 METHOXYPYRIDIN 2 YL] 9 [(1,4) 4 METHYLCYCLOHEXYL] 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; N [6 [4 (DIMETHYLAMINO)PIPERIDIN 1 YL]PYRIDAZIN 3 YL] 9 [(1,4) 4 METHYLCYCLOHEXYL] 9H PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; PALBOCICLIB; PHOSPHOTRANSFERASE INHIBITOR; PYRIDINE DERIVATIVE; PYRIDONE DERIVATIVE; PYRIDO[4',3':4,5]PYRROLO[2,3 D]PYRIMIDINE DERIVATIVE; PYRROLO[2,3 D]PYRIMIDINE DERIVATIVE; SORAFENIB; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; ASSAY; CELL DEATH; CELL PROLIFERATION; CONTROLLED STUDY; DRUG CLEARANCE; DRUG HALF LIFE; GROWTH INHIBITION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PHOSPHORYLATION; RAT; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE; XENOGRAFT;

ANIMALS; CYCLIN-DEPENDENT KINASE 4; CYCLIN-DEPENDENT KINASE 6; CYTOCHROME P-450 CYP3A; DOGS; DRUG DISCOVERY; FMS-LIKE TYROSINE KINASE 3; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; MACACA FASCICULARIS; NAPHTHYRIDINES; PROTEIN KINASE INHIBITORS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; U937 CELLS;

EID: 84899573074     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500118j     Document Type: Article

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