The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: Establishing the pharmacophore.
A series of HIV-1 integrase inhibitors containing a novel metal binding motif consisting of the 8-hydroxy-1,6-naphthyridine core and either an oxadiazole or triazole has been identified. The design of the key structural components was based on a two-metal coordination pharmacophore. This report presents initial structure-activity data that shows the new chelation architecture delivers potent inhibition in both enzymatic and antiviral assays.
Johns
Brian A
BA
Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, NC 27709, USA.
Weatherhead
Jason G
JG
Allen
Scott H
SH
Thompson
James B
JB
Garvey
Edward P
EP
Foster
Scott A
SA
Jeffrey
Jerry L
JL
Miller
Wayne H
WH
D020816:Amino Acid Motifs; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D019380:Anti-HIV Agents; D002614:Chelating Agents; D019428:HIV Integrase Inhibitors; D009287:Naphthyridines; D010069:Oxadiazoles; D014230:Triazoles