4-Hydroxy-5-pyrrolinone-3-carboxamide HIV-1 integrase inhibitors

The viral enzyme integrase is essential for the replication of HIV-1 and, after the discovery of Isentress™, represents a validated target for anti-retroviral therapy. Incorporation of the dihydroxycarbonyl pharmacophore into a pyrrolinone scaffold led to the discovery of 5-pyrrolinone-3-carboxamides as a structurally diverse class of HIV-1 integrase inhibitors.

A series of novel 4-hydroxy-5-pyrrolinone-3-carboxamide HIV-1 integrase inhibitors was identified. SAR around the pyrrolinone core resulted in the discovery of compounds with inhibitory activity in the low nanomolar range.Figure optionsDownload as PowerPoint slide