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

I Dorange, R Forsblom, I Macsari, M Svensson…

Index: Dorange, Ismet; Forsblom, Rickard; MacSari, Istvan; Svensson, Mats; Besidski, Yevgeni; Blid, Jan; Sohn, Daniel; Gravenfors, Ylva; Bylund, Johan Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 22 p. 6888 - 6895,8

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Citation Number: 10

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 ...