Synthesis and evaluation of atorvastatin esters as prodrugs metabolically activated by human carboxylesterases. Issue 3 (1st February 2016)

• Record Type: Journal Article
• Authors: Mizoi, Kenta; Takahashi, Masato; Haba, Masami; Hosokawa, Masakiyo
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 3(2016)
• Page Start: 921
• Page End: 923
• Publication Date: 2016-02-01
• Subjects: DMP 2, 2-dimethoxypropane -- TsOH p-toluenesulfonic acid -- THF tetrahydrofuran -- EDC 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide -- DMAP 4-dimethylaminopyridine; Carboxylesterase -- CES1 -- Atorvastatin -- Prodrug -- Metabolism; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.12.069
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We synthesized 11 kinds of prodrug with an esterified carboxylic acid moiety of atorvastatin in moderate to high yields. We discovered that they underwent metabolic activation specifically by the human carboxylesterase 1 (CES1) isozyme. The results suggested that these ester compounds of atorvastatin have the potential to act as prodrugs in vivo.