Design, synthesis and in vitro/in vivo evaluation of orally bioavailable prodrugs of a catechol-O-methyltransferase inhibitor
| Autor: | Marko Lehtonen, Mikko Koskinen, Jarmo Pystynen, Krista Laine, Jouko Savolainen, Jarkko Rautio, Jukka Leppänen, Mikko Sairanen |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Clinical Biochemistry Pharmaceutical Science Administration Oral Biological Availability Pharmacology COMT inhibitor Biochemistry chemistry.chemical_compound Drug Discovery Animals Humans Prodrugs In vitro in vivo Enzyme Inhibitors Rats Wistar Molecular Biology Gastrointestinal tract Catechol-O-methyl transferase Organic Chemistry Catechol O-Methyltransferase Inhibitors Prodrug Bioavailability Rats chemistry Design synthesis Drug Design Lipophilicity Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(8) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect