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

Paola Pace; Stéphane A H Spieser; Vincenzo Summa

doi:10.1016/j.bmcl.2008.06.056

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

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3865-9. doi: 10.1016/j.bmcl.2008.06.056. Epub 2008 Jun 20.

Authors

Paola Pace¹, Stéphane A H Spieser, Vincenzo Summa

Affiliation

¹ Department of Medicinal Chemistry, IRBM-MRL Rome, Via Pontina Km 30,600, 00040 Pomezia, Rome, Italy. paola_pace@merck.com

PMID: 18595690
DOI: 10.1016/j.bmcl.2008.06.056

Abstract

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.

MeSH terms

Acquired Immunodeficiency Syndrome / drug therapy
Amides / chemistry
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / pharmacology
Catalysis
Chemistry, Pharmaceutical / methods
Drug Design
HIV Integrase / chemistry*
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Models, Chemical
Molecular Structure
Pyrrolidinones / chemical synthesis*
Pyrrolidinones / pharmacology*
Structure-Activity Relationship

Substances

Amides
Anti-HIV Agents
HIV Integrase Inhibitors
Pyrrolidinones
HIV Integrase
p31 integrase protein, Human immunodeficiency virus 1