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The Lipophilicity Behavior of Three Catechol‐ O ‐methyltransferase (COMT) Inhibitors and Simple Analogues
Author(s) -
Novaroli Laura,
Bouchard Doulakas Geraldine,
Reist Marianne,
Rolando Barbara,
Fruttero Roberta,
Gasco Alberto,
Carrupt PierreAlain
Publication year - 2006
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200690007
Subject(s) - lipophilicity , chemistry , entacapone , catechol , catechol o methyl transferase , partition coefficient , stereochemistry , computational chemistry , chromatography , organic chemistry , levodopa , biochemistry , medicine , allele , disease , pathology , parkinson's disease , gene
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 Δlog P (difference between log P in two different solvent systems) and diff (log P N−I ) (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.