Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3- (6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl) pyridin-2(1H)-one (BMS-695735), an orally efficacious inhibitor of insulin-like growth factor-1 receptor kinase with broad spectrum in vivo antitumor activity

Journal of Medicinal Chemistry

Volumn 51, Issue 19, 2008, Pages 5897-5900

  Velaparthi, Upender ^a   Wittman, Mark ^a   Liu, Peiying ^a   Carboni, Joan M ^a   Lee, Francis Y ^a   Attar, Ricardo ^a   Balimane, Praveen ^a   Clarke, Wendy ^a   Sinz, Michael W ^a   Hurlburt, Warren ^a   Patel, Karishma ^a   Discenza, Lorell ^a   Kim, Sean ^a   Gottardis, Marco ^a   Greer, Ann ^a   Li, Aixin ^a   Saulnier, Mark ^a   Yang, Zheng ^a   Zimmermann, Kurt ^a   Trainor, George ^a   Vyas, Dolatrai ^a   more..

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 (4 CHLORO 1H PYRAZOL 1 YL)ETHYLAMINO] 3 [6 [1 (3 FLUOROPROPYL)PIPERIDIN 4 YL] 4 METHYL 1H BENZO[D]IMIDAZOL 2 YL] 2(1H) ONE; BENZIMIDAZOLE DERIVATIVE; CYTOCHROME P450 3A4; PIPERIDINE DERIVATIVE; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; SOMATOMEDIN C RECEPTOR; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; DRUG ACTIVITY; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; CELL LINE, TUMOR; CELL PROLIFERATION; CYTOCHROME P-450 CYP3A; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MICE; MICE, NUDE; MOLECULAR STRUCTURE; NEOPLASM TRANSPLANTATION; NEOPLASMS; PROTEIN KINASE INHIBITORS; PYRIDONES; RECEPTOR, IGF TYPE 1; RECEPTORS, STEROID; SOLUBILITY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 53549109444     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800832q     Document Type: Article

References (24)

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24. The potential disruption of glucose homeostasis by compound 10 arising from the inhibition of IR was evaluated in vivo in oral glucose tolerance test (OGTT). The test was performed in mice at both 50 and 100 mpk and found that significant glucose elevation was not observed prior to glucose challenge. However, after glucose challenge, an elevation of glucose level is observed at the 100 mpk dose that is very similar to the effect observed for compound 1 as reported in reference 10.