title: Design of second generation HIV-1 integrase inhibitors.
abstract: The prospect of HIV-1 integrase (IN) as a therapeutically viable retroviral drug target is on the verge of realization. The observed preclinical and clinical performance of beta-diketo containing and naphthyridine carboxamide compounds provides direct proof for the clinical application of IN inhibition. These validated lead compounds are useful in the design and development of second generation IN inhibitors. The results from preclinical and clinical studies on the first generation IN inhibitors reiterate a demand for novel second generation inhibitors with improved pharmacokinetic and metabolic properties. Pharmacophore-based drug design techniques facilitate the discovery of novel compounds on the basis of validated lead compounds specific for a drug target. In this article we have comprehensively reviewed the application of pharmacophore-based drug design methods in the field of IN inhibitor discovery.
authors.affiliation: Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Deng
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: D000818:Animals; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans
chemical_list: D019428:HIV Integrase Inhibitors