title: Substituted 2-pyrrolinone inhibitors of HIV-1 integrase.
abstract: The beta-diketoacid class of HIV-1 integrase (IN) inhibitors represent the first potent class of compounds specific for the strand transfer catalytic activity of the viral enzyme. Previously, utilizing a beta-diketoacid pharmacophore as a search query, we identified a substituted 2-pyrrolinone with modest IN inhibitory activity from a database of small-molecules [Dayam, R.; Sanchez, T.; Neamati, N. J. Med. Chem.2005, 48, 8009]. In efforts to optimize this class of IN inhibitors, we carried out a structure-activity relationship analysis around the 2-pyrrolinone core. Here, we present a new class of 2-pyrrolinone IN inhibitors.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Raveendra
authors.initials: R
authors.lastname: Dayam
authors.forename: Laith Q
authors.initials: LQ
authors.lastname: Al-Mawsawi
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D011760:Pyrrolidinones; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology; D000068898:Raltegravir Potassium; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005663:Furans; D019428:HIV Integrase Inhibitors; D009930:Organic Chemicals; D011758:Pyrroles; D011760:Pyrrolidinones; D015363:Quinolones; C451733:S 1360; D014230:Triazoles; D000068898:Raltegravir Potassium; C509700:elvitegravir; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1