title: Synthesis and evaluation of atorvastatin esters as prodrugs metabolically activated by human carboxylesterases.
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.
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8, Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Mizoi
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8, Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8, Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Haba
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8, Shiomi-cho, Choshi, Chiba 288-0025, Japan. Electronic address: masakiyo@cis.ac.jp.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Hosokawa
mesh_terms: D000069059:Atorvastatin / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D004952:Esters / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D004952:Esters; D011355:Prodrugs; D000069059:Atorvastatin; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human
keywords: Atorvastatin; CES1; Carboxylesterase; Metabolism; Prodrug