Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of polo-like kinase 1 (MLN0905)

Journal of Medicinal Chemistry

Volumn 55, Issue 1, 2012, Pages 197-208

  Duffey, Matthew O ^a   Vos, Tricia J ^a   Adams, Ruth ^a   Alley, Jennifer ^a   Anthony, Justin ^a   Barrett, Cynthia ^a   Bharathan, Indu ^a   Bowman, Douglas ^a   Bump, Nancy J ^a   Chau, Ryan ^a   Cullis, Courtney ^a   Driscoll, Denise L ^a   Elder, Amy ^a   Forsyth, Nancy ^a   Frazer, Jonathan ^a   Guo, Jianping ^a   Guo, Luyi ^a   Hyer, Marc L ^a   Janowick, David ^a   Kulkarni, Bheemashankar ^a   Lai, Su Jen ^a   Lasky, Kerri ^a   Li, Gang ^a   Li, Jing ^a   Liao, Debra ^a   Little, Jeremy ^a   Peng, Bo ^a   Qian, Mark G ^a   Reynolds, Dominic J ^a   Rezaei, Mansoureh ^a   Scott, Margaret Porter ^a   Sells, Todd B ^a   Shinde, Vaishali ^a   Shi, Qiuju Judy ^a   Sintchak, Michael D ^a   Soucy, Francois ^a   Sprott, Kevin T ^a   Stroud, Stephen G ^a   Nestor, Michelle ^a   Visiers, Irache ^a   Weatherhead, Gabriel ^a   Ye, Yingchun ^a   Damore, Natalie ^a   more..

^a MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 2 [3 (3 AMINOPROPYL)PHENYLAMINO] 9 CHLORO 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 2 AMINO 9 CHLORO 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 CHLORO 2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 CHLORO 2 (PHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 CHLORO 2 [5 [3 (DIMETHYLAMINO)PROPYL] 2 (TRIFLUOROMETHOXY)PHENYLAMINO] 5H BENZO[B]PYRIMIDO[4,5 D]AZEPINE 6(7H) THIONE; 9 CHLORO 2 [5 [3 (DIMETHYLAMINO)PROPYL] 2 METHYLPHENYLAMINO] 5H BENZO[B]PYRIMIDO[4,5 D]AZEPINE 6(7H) THIONE; 9 CHLORO 2 [[2 CHLORO 5 [3 (DIMETHYLAMINO)PROPYL]PHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[3 [3 (DIMETHYLAMINO)PROPYL] 2 METHOXYPHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[3 [3 (DIMETHYLAMINO)PROPYL] 4 (TRIFLUOROMETHYL)PHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[3 [3 (DIMETHYLAMINO)PROPYL] 4 FLUOROPHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[3 [3 (DIMETHYLAMINO)PROPYL] 4 METHOXYPHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[3 [3 (DIMETHYLAMINO)PROPYL]PHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[3 CHLORO 5 [3 (DIMETHYLAMINO)PROPYL]PHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[5 [3 (DIMETHYLAMINO)PROPYL] 2 (TRIFLUOROMETHOXY)PHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[5 [3 (DIMETHYLAMINO)PROPYL] 2 ISOPROPYLPHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[5 [3 (DIMETHYLAMINO)PROPYL] 2 METHOXYPHENYL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[5 [3 (DIMETHYLAMINO)PROPYL] 2 METHYLPYRIDIN 3 YL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CHLORO 2 [[5 [3 (DIMETHYLAMINO)PROPYL]PYRIDIN 3 YL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; 9 CYANO 2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 FLUORO 2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 IODO 2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 METHYL 2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 TRIFLUOROMETHYL 2 (3,4 DIMETHOXYPHENYLAMINO) 5H BENZO[B]PYRIMIDO[4,5 D]AZEPIN 6(7H) ONE; 9 TRIFLUOROMETHYL 2 [[5 [3 (DIMETHYLAMINO)PROPYL] 2 METHYLPYRIDIN 3 YL]AMINO] 5,7 DIHYDRO 6H PYRIMIDO[5,4 D][1]BENZAZEPINE 6 THIONE; ANTINEOPLASTIC AGENT; LACTAM DERIVATIVE; MLN 0905; POLO LIKE KINASE 1; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CANCER REGRESSION; CELL VIABILITY; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; DRUG TRANSFORMATION; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MITOSIS INHIBITION; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; RAT; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; BENZAZEPINES; BIOLOGICAL AVAILABILITY; CELL CYCLE PROTEINS; CELL LINE, TUMOR; CELL SURVIVAL; CRYSTALLOGRAPHY, X-RAY; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; LACTAMS; MICE; MICE, NUDE; MITOSIS; MODELS, MOLECULAR; NEOPLASM TRANSPLANTATION; PROTEIN CONFORMATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; THIONES; TRANSPLANTATION, HETEROLOGOUS;

EID: 84862967638     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2011172     Document Type: Article

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