Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

Giang Le; Nick Vandegraaff; David I Rhodes; Eric D Jones; Jonathan A V Coates; Long Lu; Xinming Li; Changjiang Yu; Xiao Feng; John J Deadman

doi:10.1016/j.bmcl.2010.07.041

Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5013-8. doi: 10.1016/j.bmcl.2010.07.041. Epub 2010 Jul 16.

Authors

Giang Le¹, Nick Vandegraaff, David I Rhodes, Eric D Jones, Jonathan A V Coates, Long Lu, Xinming Li, Changjiang Yu, Xiao Feng, John J Deadman

Affiliation

¹ Avexa Ltd, 576 Swan Street, Richmond, Victoria 3121, Australia.

PMID: 20685117
DOI: 10.1016/j.bmcl.2010.07.041

Abstract

A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.

MeSH terms

Drug Discovery
Drug Resistance, Viral / genetics
HIV / drug effects
HIV / genetics
HIV Integrase Inhibitors / chemistry*
HIV Integrase Inhibitors / pharmacology*
Mutation
Pyrrolidinones / pharmacology*
Raltegravir Potassium
Structure-Activity Relationship

Substances

HIV Integrase Inhibitors
Pyrrolidinones
Raltegravir Potassium