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ID: ALA1156974
Journal: Bioorg Med Chem Lett
Title: Design, synthesis and in vitro/in vivo evaluation of orally bioavailable prodrugs of a catechol-O-methyltransferase inhibitor.
Authors: Rautio J, Leppänen J, Lehtonen M, Laine K, Koskinen M, Pystynen J, Savolainen J, Sairanen M.
Abstract: Compound 1 is an investigational, nanomolar inhibitor of catechol-O-methyltransferase (COMT) that suffers from poor oral bioavailability, most probably due to its low lipophilicity throughout most of the gastrointestinal tract and, to a lesser extent, its rapid systemic clearance. Several lipophilic esters were designed as prodrugs and synthesized in an attempt to optimize presystemic drug absorption. A modest twofold increase in 6-h exposure of 1 was observed with two prodrugs, compared to that of 1, after oral treatment in rats.
CiteXplore: 20231095