A series of 5-aminosubstituted 4-fluorobenzyl-8-hydroxy-[1,6]naphthyridine-7-carboxamide HIV-1 integrase inhibitors

James P Guare; John S Wai; Robert P Gomez; Neville J Anthony; Samson M Jolly; Amanda R Cortes; Joseph P Vacca; Peter J Felock; Kara A Stillmock; William A Schleif; Gregory Moyer; Lori J Gabryelski; Lixia Jin; I-Wu Chen; Daria J Hazuda; Steven D Young

doi:10.1016/j.bmcl.2006.03.003

A series of 5-aminosubstituted 4-fluorobenzyl-8-hydroxy-[1,6]naphthyridine-7-carboxamide HIV-1 integrase inhibitors

Bioorg Med Chem Lett. 2006 Jun 1;16(11):2900-4. doi: 10.1016/j.bmcl.2006.03.003. Epub 2006 Mar 22.

Authors

James P Guare¹, John S Wai, Robert P Gomez, Neville J Anthony, Samson M Jolly, Amanda R Cortes, Joseph P Vacca, Peter J Felock, Kara A Stillmock, William A Schleif, Gregory Moyer, Lori J Gabryelski, Lixia Jin, I-Wu Chen, Daria J Hazuda, Steven D Young

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. jim_guare@merck.com

PMID: 16554152
DOI: 10.1016/j.bmcl.2006.03.003

Abstract

A series of 5-amino derivatives of 8-hydroxy[1,6]-naphthyridine-7-carboxamide exhibiting sub-micromolar potency against replication of HIV-1 in cell culture was identified. One of these analogs, compound 12, displayed excellent pharmacokinetic properties when dosed orally in rats and in monkeys. This compound was demonstrated to be efficacious against replication of simian-human immunodeficiency virus (SHIV) 89.6P in infected rhesus macaques.

MeSH terms

Amination
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / chemistry
HIV Integrase Inhibitors / pharmacology*
Molecular Structure
Naphthyridines / chemical synthesis
Naphthyridines / chemistry*
Naphthyridines / pharmacology*
Structure-Activity Relationship

Substances

HIV Integrase Inhibitors
Naphthyridines