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.

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

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

Affiliation

Velaparthi U; Discovery Chemistry, Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Co., Wallingford, Connecticut 06492, USA. upender.velaparthi@bms.com

J Med Chem ; 51(19): 5897-900, 2008 Oct 09.

Article in En | MEDLINE | ID: mdl-18763755

Subject(s)

Antineoplastic Agents/administration & dosage; Antineoplastic Agents/pharmacology; Benzimidazoles/administration & dosage; Benzimidazoles/pharmacology; Neoplasms/drug therapy; Protein Kinase Inhibitors/administration & dosage; Protein Kinase Inhibitors/pharmacology; Pyridones/administration & dosage; Pyridones/pharmacology; Receptor, IGF Type 1/antagonists & inhibitors; Administration, Oral; Animals; Antineoplastic Agents/chemistry; Benzimidazoles/chemistry; Cell Line, Tumor; Cell Proliferation/drug effects; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Screening Assays, Antitumor; Humans; Mice; Mice, Nude; Molecular Structure; Neoplasm Transplantation; Pregnane X Receptor; Protein Kinase Inhibitors/chemistry; Pyridones/chemistry; Receptors, Steroid/drug effects; Receptors, Steroid/metabolism; Solubility; Stereoisomerism; Structure-Activity Relationship; Xenograft Model Antitumor Assays

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyridones / Benzimidazoles / Receptor, IGF Type 1 / Protein Kinase Inhibitors / Neoplasms / Antineoplastic Agents Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2008 Type: Article Affiliation country: United States

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