title: Azido-containing aryl beta-diketo acid HIV-1 integrase inhibitors.
abstract: Aryl beta-diketo acids (ADK) comprise a general class of potent HIV-1 integrase (IN) inhibitors, which can exhibit selective inhibition of strand transfer reactions in extracellular recombinant IN assays and provide potent antiviral effects in HIV-infected cells. Recent studies have shown that polycyclic aryl or aryl rings bearing aryl-containing substituents are components of potent members of this class. Reported herein is the first use of azido functionality as an aryl replacement in beta-diketo acid IN inhibitors. The ability of azido-containing inhibitors to exhibit potent inhibition of IN and antiviral protection in HIV-infected cells, renders the azide group of potential value in the further development of ADK-based IN inhibitors.
authors.affiliation: Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MD, USA.
authors.forename: Xuechun
authors.initials: X
authors.lastname: Zhang
authors.forename: Godwin C G
authors.initials: GC
authors.lastname: Pais
authors.forename: Evguenia S
authors.initials: ES
authors.lastname: Svarovskaia
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
authors.forename: Allison A
authors.initials: AA
authors.lastname: Johnson
authors.forename: Rajeshri G
authors.initials: RG
authors.lastname: Karki
authors.forename: Marc C
authors.initials: MC
authors.lastname: Nicklaus
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Pathak
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001386:Azides / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006678:HIV / Q000187:drug effects; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007651:Keto Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001386:Azides; D019428:HIV Integrase Inhibitors; D007202:Indicators and Reagents; D007651:Keto Acids; D011994:Recombinant Proteins; D019427:HIV Integrase