1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position

Brian A Johns; Jason G Weatherhead; Scott H Allen; James B Thompson; Edward P Garvey; Scott A Foster; Jerry L Jeffrey; Wayne H Miller

doi:10.1016/j.bmcl.2009.01.089

1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1807-10. doi: 10.1016/j.bmcl.2009.01.089. Epub 2009 Jan 30.

Authors

Brian A Johns¹, Jason G Weatherhead, Scott H Allen, James B Thompson, Edward P Garvey, Scott A Foster, Jerry L Jeffrey, Wayne H Miller

Affiliation

¹ Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, NC 27709, USA.

PMID: 19217284
DOI: 10.1016/j.bmcl.2009.01.089

Abstract

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.

MeSH terms

Amino Acid Motifs
Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Chelating Agents / pharmacology
Chemistry, Pharmaceutical / methods*
Drug Design
HIV Infections / drug therapy
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / pharmacology
Humans
Metals / chemistry
Models, Chemical
Molecular Structure
Naphthyridines / chemical synthesis*
Naphthyridines / pharmacology
Oxadiazoles / chemistry*
Structure-Activity Relationship
Triazoles / chemistry*

Substances

Anti-HIV Agents
Chelating Agents
HIV Integrase Inhibitors
Metals
Naphthyridines
Oxadiazoles
Triazoles