Discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin- 6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (TAK-593), a highly potent VEGFR2 kinase inhibitor

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 8, 2013, Pages 2333-2345

  Miyamoto, Naoki ^a   Sakai, Nozomu ^a   Hirayama, Takaharu ^a   Miwa, Kazuhiro ^a   Oguro, Yuya ^a   Oki, Hideyuki ^a   Okada, Kengo ^a   Takagi, Terufumi ^a   Iwata, Hidehisa ^a   Awazu, Yoshiko ^a   Yamasaki, Seiji ^a   Takeuchi, Toshiyuki ^a   Miki, Hiroshi ^a   Hori, Akira ^a   Imamura, Shinichi ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Imidazo 1,2 b pyridazine; Kinase inhibitor; VEGF; VEGFR2

Indexed keywords

3 FLUORO N [3 [[2 [[[3 (TRIFLUOROMETHYL)PHENYL]CARBONYL]AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL]BENZAMIDE; ACYLAMINO 6 PHENOXYIMIDAZO[1,2 B]PYRIDAZINE DERIVATIVE; IMIDAZO[1,2-B]PYRIDAZINE DERIVATIVE; IMIDAZOPYRIDINE DERIVATIVE; N [3 [[2 (ACETYLAMINO)IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 3 FLUOROBENZAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 1 METHYL 1H 1,2,3 TRIAZOLE 5 CARBOXAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 1,3 DIMETHYL 1H PYRAZOLE 5 CARBOXAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 1,5 DIMETHYL 1H PYRAZOLE 3 CARBOXAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 3 FLUOROBENZAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 3 METHYLISOXAZOLE 5 CARBOXAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL]CYCLOPROPANECARBOXAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL]ISOXAZOLE 5 CARBOXAMIDE; N [3 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL]PYRIDINE 4 CARBOXAMIDE; N [5 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY] 2 ETHYLPHENYL] 1,3 DIMETHYL 1H PYRAZOLE 5 CARBOXAMIDE; N [5 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY] 2 FLUOROPHENYL] 1,3 DIMETHYL 1H PYRAZOLE 5 CARBOXAMIDE; N [5 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY] 2 METHYLPHENYL] 1,3 DIMETHYL 1H PYRAZOLE 5 CARBOXAMIDE; N [5 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]LPHENYL] 3 FLUOROBENZAMIDE; N [5 [[2 [(CYCLOPROPYLCARBONYL)AMINO]IMIDAZO[1,2 B]PYRIDAZIN 6 YL]OXY]PHENYL] 1,3 DIMETHYL 1H PYRAZOLE 5 CARBOXAMIDE; N [6 [3 [( FLUOROPHENYLCARBONYL)AMINO]PHENOXY]IMIDAZO[1,2 B]PYRIDAZIN 2 YL] 3 METHYLTHIOPHENE 2 CARBOXAMIDE; N [6 [3 [( FLUOROPHENYLCARBONYL)AMINO]PHENOXY]IMIDAZO[1,2 B]PYRIDAZIN 2 YL]TETRAHYDRO 2H PYRAN 4 CARBOXAMIDE; N [6 [3 [(2,2 DIMETHYLPROPANOYL)AMINO]PHENOXY]IMIDAZO[1,2 B]PYRIDAZIN 2 YL]CYCLOPROPANECARBOXAMIDE; N [6 [3 [[[3 (TRIFLUOROMETHYL)PHENYL]CARBONYL]AMINO]PHENOXY]IMIDAZO[1,2 B]PYRIDAZIN 2 YL]TETRAHYDRO 2H PYRAN 4 CARBOXAMIDE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR KINASE; PYRIDAZINE DERIVATIVE; TAK 593; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR; VASCULOTROPIN RECEPTOR KINASE;

ANIMAL EXPERIMENT; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG DESIGN; DRUG METABOLISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HYBRIDIZATION; IC 50; LUNG ADENOCARCINOMA; MALE; NONHUMAN; RAT; TUMOR XENOGRAFT; UMBILICAL VEIN ENDOTHELIAL CELL;

AMINOIMIDAZOLE CARBOXAMIDE; ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; MACACA FASCICULARIS; MALE; MICE; MICE, INBRED AKR; MICE, NUDE; MODELS, MOLECULAR; PROTEIN KINASE INHIBITORS; PYRAZOLES; RATS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84875754075     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2013.01.074     Document Type: Article

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