1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position.
The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.
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; D008670:Metals / Q000737:chemistry; 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*
D019380:Anti-HIV Agents; D002614:Chelating Agents; D019428:HIV Integrase Inhibitors; D008670:Metals; D009287:Naphthyridines; D010069:Oxadiazoles; D014230:Triazoles