Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Discovery of novel pyrrolopyridazine scaffolds as transient receptor potential vanilloid (TRPV1) antagonists.

Authors: Ismet Dorange, Rickard Forsblom, Istvan Macsari, Mats Svensson, Johan Bylund, Yevgeni Besidski, Jan Blid, Daniel Sohn, Ylva Gravenfors

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Nov 15 , 22, 6888-95

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23058884

Abstract
A novel indolizine class of compounds was identified as TRPV1 antagonist from an HTS campaign. However, this indolizine class proved to be unstable and reacted readily with glutathione when exposed to light and oxygen. Reactivity was reduced by the introduction of a nitrogen atom alpha to the indolizine nitrogen. The pyrrolopyridazine core obtained proved to be inert to the action of light and oxygen. The synthesis route followed the one used for the indolizine compounds, and the potency and ADMET profile proved to be similar.