Discovery of (S)-1-(1-(Imidazo[1,2- a ]pyridin-6-yl)ethyl)-6-(1-methyl-1 H -pyrazol-4-yl)-1 H -[1,2,3]triazolo[4,5- b ]pyrazine (Volitinib) as a Highly Potent and Selective Mesenchymal-Epithelial Transition Factor (c-Met) Inhibitor in Clinical Development for Treatment of Cancer

Journal of Medicinal Chemistry

Volumn 57, Issue 18, 2014, Pages 7577-7589

  Jia, Hong ^a   Dai, Guangxiu ^a   Weng, Jianyang ^a   Zhang, Zhulin ^a   Wang, Qing ^a   Zhou, Feng ^a   Jiao, Longxian ^a   Cui, Yumin ^a   Ren, Yongxin ^a   Fan, Shiming ^a   Zhou, Jinghong ^a   Qing, Weiguo ^a   Gu, Yi ^a   Wang, Jian ^a   Sai, Yang ^a   Su, Weiguo ^a  

^a Hutchison MediPharma Limited   (China)

Author keywords

[No Author keywords available]

Indexed keywords

1 (IMIDAZO[1,2 A]PYRAZIN 6 YLMETHYL) 6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 (IMIDAZO[1,2 A]PYRIDIN 6 YLMETHYL) 6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 (IMIDAZO[1,2 A]PYRIDIN 6 YLMETHYL) 6 [1 (2,2,2 TRIFLUOROETHYL) 1H PYRAZOL 4 YL] 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 (IMIDAZO[1,2 B]PYRIDAZIN 6 YLMETHYL) 6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 (PYRAZOLO[1,5 A]PYRIDIN 5 YLMETHYL) 6 [1 (2,2,2TRIFLUOROETHYL) 1H PYRAZOL 4 YL] 1H [1,2,3]TRAZOLO[4,5 B]PYRAZINE; 1 ([1,2,4]TRIAZOLO[1,5 A]PYRIDIN 6 YLMETHYL) 6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 ([1,2,4]TRIAZOLO[1,5 A]PYRIDIN 7 YLMETHYL) 6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 [(1H PYRAZOLO[3,4 B]PYRIDIN 3 YL)METHYL] 6 (1 METHYL 1 H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 1 [(1H PYRAZOLO[3,4 B]PYRIDIN 3 YL)METHYL] 6 [1 (2,2,2 TRIFLUOROETHYL) 1H PYRAZOL 4 YL] 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 2 [(6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 1 YL)METHYL]THIENOL[2,3 B]PYRIDINE; 2 [4 (1 ((1H PYRAZOLO[3,4 B]PYRIDIN 3 YL)METHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 6 YL) 1H PYRAZOL 1 YL]ETHANOL; 2 [4 (1 ((1H PYRROLO[2,3 B]PYRIDIN 2 YL)METHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 6 YL) 1H PYRAZOL 1 YL]ETHANOL; 2 [4 (1 ((1H PYRROLO[2,3 B]PYRIDIN 3 YL)METHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 6 YL) 1H PYRAZOL 1 YL]ETHANOL; 2 [4 (1 (PYRAZOLO[1,5 A]PYRIDIN 5 YLMETHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 6 YL) 1H PYRAZOL 1 YL]ETHANOL; 3 [(6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 1 YL)METHYL]THIENOL[2,3 B]PYRIDINE; 5 [(6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 1 YL)METHYL] 1H THIENOL[3,2 C]PYRAZOLE; 5 [1 (IMIDAZO[1,2 A]PYRIDIN 6 YLMETHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 6 YL)PICOLINONITRILE; 6 (1 METHYL 1H PYRAZOL 4 YL) 1 (PYRAZOLO[1,5 A]PYRIDIN 5 YLMETHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 6 (1 METHYL 1H PYRAZOL 4 YL) 1 (PYRAZOLO[1,5 A]PYRIMIDIN 5 YLMETHYL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZINE; 6 [(5 (1 METHYL 1H PYRAZOL 4 YL) 3H IMIDAZO[4,5 B]PYRIDIN 3 YL)METHYL]QUINOLINE; 6 [(5 (1 METHYL 1H PYRAZOL 4 YL) 3H [1,2,3]TRIAZOLO[4,5 B]PYRIDIN 3 YL)METHYL]QUINOLINE; 6 [(5 (1 METHYL 1H PYRAZOL 4 YL) 3H [1,2,3]TRIAZOLO[4,5 D]PYRIMIDIN 3 YL)METHYL]QUINOLINE; 6 [(6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRAZIN 1 YL)METHYL]QUINOLINE; 6 [(6 (1 METHYL 1H PYRAZOL 4 YL) 1H [1,2,3]TRIAZOLO[4,5 B]PYRIDIN 1 YL)METHYL]QUINOLINE; 6 [(6 (1 METHYL 1H PYRAZOL 4 YL) [1,2,4]TRIAZOLO[4,3 B]PYRIDAZIN 3 YL)METHYL]QUINOLONE; 6-[(6 (1 METHYL 1H PYRAZOL 4 YL) 1H IMIDAZO [4,5 B]PYRAZIN 1 YL)METHYL]QUINOLINE; ANTINEOPLASTIC AGENT; PYRAZINE DERIVATIVE; SAVOLITINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; 1-(1-(IMIDAZO(1,2-A)PYRIDIN-6-YL)ETHYL)-6-(1-METHYL-1H-PYRAZOL-4-YL)-1H-(1,2,3)TRIAZOLO(4,5-B)PYRAZINE; ADENOSINE TRIPHOSPHATE; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE; SCATTER FACTOR RECEPTOR; TRIAZINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; ENZYMATIC ASSAY; ENZYME PHOSPHORYLATION; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; MOUSE; NEOPLASM; NONHUMAN; NUDE MOUSE; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME; ANIMAL; ANTAGONISTS AND INHIBITORS; BINDING COMPETITION; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; DRUG SCREENING; ENZYME SPECIFICITY; HUMAN; IC50; METABOLISM; PROTEIN CONFORMATION; TUMOR CELL LINE;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTINEOPLASTIC AGENTS; BINDING, COMPETITIVE; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG DISCOVERY; FEMALE; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MET; PYRAZINES; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; TRIAZINES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84907573581     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500510f     Document Type: Article

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