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The Lipophilicity Behavior of Three Catechol-O-methyltransferase (COMT) Inhibitors and Simple Analogues

✍ Scribed by Laura Novaroli; Geraldine Bouchard Doulakas; Marianne Reist; Barbara Rolando; Roberta Fruttero; Alberto Gasco; Pierre-Alain Carrupt

Publisher
John Wiley and Sons
Year
2006
Tongue
German
Weight
141 KB
Volume
89
Category
Article
ISSN
0018-019X

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✦ Synopsis

The ionization and lipophilicity properties of the second-generation catechol-O-methyltransferase (COMT) inhibitors entacapone (1), nitecapone (2), and tolcapone (3) which share the same nitrocatechol structure but have remarkably different pharmacokinetic profiles are investigated to identify relationships between some of these physicochemical parameters and the blood-brain-barrier (BBB) passage. In addition, the lipophilicity behavior of the simpler, structurally related analogues 4 -11 is studied. Combined descriptors such as Dlog P (difference between log P in two different solvent systems) and diff(log P NÀI ) (difference between log P of two different electrical forms of a given solute in the same system) provide insight into inter-and intramolecular interactions characteristic of the analyzed compounds.

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