Channelpedia

PubMed 19394229


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.2



Title: 2,4(5)-diarylimidazoles as inhibitors of hNaV1.2 sodium channels: pharmacological evaluation and structure-property relationships.

Authors: Marco Fantini, Mirko Rivara, Valentina Zuliani, Christopher L Kalmar, Federica Vacondio, Claudia Silva, Aparna R Baheti, Natasha Singh, Ellen C Merrick, Ravi S Katari, Giuseppe Cocconcelli, Chiara Ghiron, Manoj K Patel

Journal, date & volume: Bioorg. Med. Chem., 2009 May 15 , 17, 3642-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19394229


Abstract
Sodium (Na) channels continue to represent an important target for the development of novel anticonvulsants. We have synthesized and evaluated a series of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na(V)1.2 Na channel isoform. Starting with the unsubstituted lead compound previously published 3, SAR studies were performed introducing substituents with different physico-chemical properties. Lipophilicity (log D(7.4)) and basicity (pK(a)) of the compounds were measured and submitted for QSPR investigations. Some of the active compounds described had IC(50) values that were considerably lower than our lead compound. In particular, the m-CF(3) disubstituted 22 was the most active compound, inhibiting hNa(V)1.2 currents within the nanomolar concentration range (IC(50)=200 nM). In comparison, lamotrigine and phenytoin, two clinically used anticonvulsant drugs known to inhibit Na channels, had IC(50)'s values that were greater than 100 microM.