Design, synthesis and in vitro/in vivo evaluation of orally bioavailable prodrugs of a catechol-O-methyltransferase inhibitor

被引：13

作者：

Rautio, Jarkko ^{[1
]}

Leppanen, Jukka ^{[1
]}

Lehtonen, Marko ^{[1
]}

Laine, Krista ^{[1
]}

Koskinen, Mikko ^{[2
]}

Pystynen, Jarmo ^{[2
]}

Savolainen, Jouko ^{[3
]}

Sairanen, Mikko ^{[2
]}

机构：

[1] Univ Eastern Finland, Sch Pharm, FI-70211 Kuopio, Finland

[2] Orion Corp, Orion Pharma, FI-20101 Turku, Finland

[3] Fennopharma Ltd, FI-70210 Kuopio, Finland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 08期

基金：

芬兰科学院;

关键词：

Prodrug; COMT inhibitor; Oral bioavailability; PARKINSONS-DISEASE; PHARMACOKINETICS; BACAMPICILLIN; BIOCONVERSION; PARAOXONASE; ENTACAPONE; HYDROLYSIS; ABSORPTION; AMPICILLIN; PEPTIDE;

D O I：

10.1016/j.bmcl.2010.02.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compound 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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2614 / 2616

页数：3

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