Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors: 2. Synthesis and characterization of a novel imide-type prodrug for improving oral absorption

Bioorganic and Medicinal Chemistry

Volumn 20, Issue 15, 2012, Pages 4680-4692

  Okaniwa, Masanori ^a   Imada, Takashi ^a   Ohashi, Tomohiro ^a   Miyazaki, Tohru ^a   Arita, Takeo ^a   Yabuki, Masato ^a   Sumita, Akihiko ^a   Tsutsumi, Shunichirou ^a   Higashikawa, Keiko ^a   Takagi, Terufumi ^a   Kawamoto, Tomohiro ^a   Inui, Yoshitaka ^a   Yoshida, Sei ^a   Ishikawa, Tomoyasu ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Imide type prodrug; Oral absorption; RAF; VEGFR2

Indexed keywords

2 CHLORO 3 (CYANOCYCLOPROPYL) N (CYCLOPROPYLCARBONYL) N [5 [[2 [(2 CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4 B]PYRIDIN 4 YL]OXY] 2 FLUOROPHENYL]BENZAMIDE; 2 CHLORO 3 (CYANOCYCLOPROPYL) N [5 [[2 [(CYCLOPROPYLCARBONYL)AMINO]AMINO[1,3]THIAZOLO[5,4B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]BENZAMIDE; 2 FLUORO 5 [(NITROPYRIDIN 2 YL)OXYL]ANILINE; ANTINEOPLASTIC AGENT; ETHYL [[2 CHLORO 3 (1 CYANOCYCLOPROPYL)PHENYL]CARBONYL][5 [[2 [(2 CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4 B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]CARBAMATE; IMIDE; N [5 [[2 (ACETYLAMINO)[1,3]THIAZOLO[5,4]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL] 2 CHLORO 3 (1 CYANOCYCLOPROPYL)BENZAMIDE; PRODRUG; TERT BUTYL [5 [(AMINOPYRIDIN 2 YL)OXY] 2 FLUOROPHENYL]CARBAMATE; TERT BUTYL [5 [[2 (CYCLOPROPYLCARBONYL)AMINO[1,3]THIAZOLO[5,4 B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]CARBAMATE; TERT BUTYL [[2 CHLORO 3 (1 CYANOCYCLOPROPYL)PHENYL]CARBONYL][5 [[2 [(2 CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4 B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]CARBAMATE ACETIC ACID; TERT BUTYL [[2 CHLORO 3 (1 CYANOCYCLOPROPYL)PHENYL]CARBONYL][5 [[2 [(2 CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4 B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]CARBAMATE ETHANOL; TERT BUTYL [[2 CHLORO 3 (1 CYANOCYCLOPROPYL)PHENYL]CARBONYL][5 [[2 [(2 CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4 B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]CARBAMATE MONOHYDRATE; TERT BUTYL [[5 (2 AMINO[1,3]THIAZOLO[5,4B]PYRIDIN 5 YL)OXY] 2 FLUOROPHENYL]CARBAMATE; TERT BUTYL [[5 [2 (ACETYLAMINO)[1,3]THIAZOLO[5,4B]PYRIDIN 5 YL]OXY] 2 FLUOROPHENYL]CARBAMATE; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG DESIGN; DRUG EFFICACY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROGEN BOND; MELANOMA; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; TREATMENT RESPONSE;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; FEMALE; HAPLORHINI; HUMANS; IMIDES; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PRODRUGS; PROTEIN KINASE INHIBITORS; RATS; RATS, NUDE; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; XENOGRAFT MODEL ANTITUMOR ASSAYS;

CANIS FAMILIARIS; MUS; RATTUS;

EID: 84863987371     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.06.015     Document Type: Article

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