title: Development of the next generation of HIV-1 integrase inhibitors: pyrazolone as a novel inhibitor scaffold.
abstract: HIV-1 integrase (IN), one of the essential enzymes in HIV infection, has been validated as a target for HIV treatment. While more than 20 drugs have been approved by the FDA to treat HIV/AIDS, only one drug, Raltegravir (1), was approved as an IN inhibitor. The rapid mutation of the virus, which leads to multidrug resistant HIV strains, presents an urgent need to find potent compounds that can serve as second-generation IN inhibitors. The pyrazolone scaffold, predicted by a computational modeling study using GS-9137(2) as a pharmacophoric model, has shown to inhibit the IN catalytic activities in low micromolar range. We have synthesized various analogs based on the pyrazolone scaffold and performed SAR studies. This paper will showcase the up-to-date result of this scaffold as a promising HIV-1 IN inhibitor.
authors.affiliation: Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, Los Angeles, CA 90089, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: Hadi
authors.forename: Yung-Hyo
authors.initials: YH
authors.lastname: Koh
authors.forename: Tino Wilson
authors.initials: TW
authors.lastname: Sanchez
authors.forename: Danielle
authors.initials: D
authors.lastname: Barrios
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.forename: Kyung Woon
authors.initials: KW
authors.lastname: Jung
mesh_terms: D002384:Catalysis; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D047069:Pyrazolones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D047069:Pyrazolones; C038362:pyrazolone