(3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1h-1,2,4-triazol-5-yl)amino)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoic acid (BMS-644950): a rationally designed orally efficacious 3-hydroxy-3-methylglutaryl coenzyme-a reductase inhibitor with reduced myotoxicity potential.

Ahmad, Saleem; Madsen, Cort S; Stein, Philip D; Janovitz, Evan; Huang, Christine; Ngu, Khehyong; Bisaha, Sharon; Kennedy, Lawrence J; Chen, Bang-Chi; Zhao, Rulin; Sitkoff, Doree; Monshizadegan, Hossain; Yin, Xiaohong; Ryan, Carol S; Zhang, Rongan; Giancarli, Mary; Bird, Eileen; Chang, Ming; Chen, Xing; Setters, Robert; Search, Debra; Zhuang, Shaobin; Nguyen-Tran, Van; Cuff, Carolyn A; Harrity, Thomas; Darienzo, Celia J; Li, Tong; Reeves, Richard A; Blanar, Michael A; Barrish, Joel C; Zahler, Robert; Robl, Jeffrey A

Ahmad, Saleem; Madsen, Cort S; Stein, Philip D; Janovitz, Evan; Huang, Christine; Ngu, Khehyong; Bisaha, Sharon; Kennedy, Lawrence J; Chen, Bang-Chi; Zhao, Rulin; Sitkoff, Doree; Monshizadegan, Hossain; Yin, Xiaohong; Ryan, Carol S; Zhang, Rongan; Giancarli, Mary; Bird, Eileen; Chang, Ming; Chen, Xing; Setters, Robert; Search, Debra; Zhuang, Shaobin; Nguyen-Tran, Van; Cuff, Carolyn A; Harrity, Thomas; Darienzo, Celia J; Li, Tong; Reeves, Richard A; Blanar, Michael A; Barrish, Joel C; Zahler, Robert; Robl, Jeffrey A.

Affiliation

Ahmad S; Bristol-Myers Squibb Research & Development, P.O. Box 4000, Princeton, New Jersey 08543, USA. saleem.ahmad@bms.com

J Med Chem ; 51(9): 2722-33, 2008 May 08.

Article in En | MEDLINE | ID: mdl-18412317

Subject(s)

Hydroxymethylglutaryl CoA Reductases/metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemical synthesis; Pyrimidines/chemical synthesis; Triazoles/chemical synthesis; Administration, Oral; Animals; Biological Availability; Chemical and Drug Induced Liver Injury/etiology; Cholesterol/biosynthesis; Cholesterol/blood; Crystallography, X-Ray; Dogs; Female; Guinea Pigs; Haplorhini; Humans; Hydroxymethylglutaryl CoA Reductases/chemistry; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors/toxicity; In Vitro Techniques; Liver/drug effects; Liver/metabolism; Models, Molecular; Muscle Cells/cytology; Muscle Cells/drug effects; Muscle Cells/metabolism; Pyrimidines/pharmacology; Pyrimidines/toxicity; Rats; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship; Triazoles/pharmacology; Triazoles/toxicity

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyrimidines / Triazoles / Hydroxymethylglutaryl-CoA Reductase Inhibitors / Hydroxymethylglutaryl CoA Reductases Type of study: Etiology_studies Limits: Animals / Female / Humans Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2008 Type: Article Affiliation country: United States

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