title: 4-Hydroxy-5-pyrrolinone-3-carboxamide HIV-1 integrase inhibitors.
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.
authors.affiliation: Department of Medicinal Chemistry, IRBM-MRL Rome, Via Pontina Km 30,600, 00040 Pomezia, Rome, Italy. paola_pace@merck.com
authors.forename: Paola
authors.initials: P
authors.lastname: Pace
authors.forename: Stéphane A H
authors.initials: SA
authors.lastname: Spieser
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Summa
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000577:Amides / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1