849470-59-3Relevant articles and documents
Development of a scaleable process for the synthesis of a next-generation statin
Hobson, Lindsay A.,Akiti, Otute,Deshmukh, Subodh S.,Harper, Shannon,Katipally, Kishta,Lai, Chiajen J.,Livingston, Robert C.,Lo, Ehrlic,Miller, Michael M.,Ramakrishnan, Srividya,Shen, Lifen,Spink, Jan,Tummala, Srinivas,Wei, Chenkou,Yamamoto, Kana,Young, John,Parsons Jr., Rodney L.
scheme or table, p. 441 - 458 (2011/04/22)
This manuscript details the process research and development of a convergent and safe approach to 1 on a multikilo scale. Specific highlights of the process development efforts will be described, including the development of a dehydrogenation method for d
(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 wi
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.
, p. 2722 - 2733 (2008/12/22)
3-Hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) inhibitors, more commonly known as statins, represent the gold standard in treating hypercholesterolemia. Although statins are regarded as generally safe, they are known to cause myopathy and, in rare
PYRIMIDINE AND PYRIDINE DERIVATIVES USEFUL AS HMG-COA REDUCTASE INHIBITORS AND METHOD OF PREPARATION THEREOF
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Page/Page column 54-55, (2010/02/11)
Compounds are provided having the following structure which are HMG CoA reductase inhibitors and thus are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids, for example, lowering LDL cholesterol and/or increasing HDL cholesterol
Synthesis and biological activity of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates, a novel series of HMG-CoA reductase inhibitors
Watanabe, Masamichi,Koike, Haruo,Ishiba, Teruyuki,Okada, Tetsuo,Seo, Shujiro,Hirai, Kentaro
, p. 437 - 444 (2007/10/03)
A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy- (E)-6-heptenoate (3a, S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin.