Design of a series of bicyclic HIV-1 integrase inhibitors. Part 2: azoles: effective metal chelators

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

doi:10.1016/j.bmcl.2010.07.081

Design of a series of bicyclic HIV-1 integrase inhibitors. Part 2: azoles: effective metal chelators

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5909-12. doi: 10.1016/j.bmcl.2010.07.081. Epub 2010 Jul 27.

Authors

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

Affiliation

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

PMID: 20727753
DOI: 10.1016/j.bmcl.2010.07.081

Abstract

Synthesis of a diverse set of azoles and their utilizations as an amide isostere in the design of HIV integrase inhibitors is described. The Letter identified thiazole, oxazole, and imidazole as the most promising heterocycles. Initial SAR studies indicated that these novel series of integrase inhibitors are amenable to lead optimization. Several compounds with low nanomolar inhibitory potency are reported.

MeSH terms

Azoles / chemical synthesis
Azoles / chemistry*
Azoles / pharmacology
Bridged Bicyclo Compounds / chemical synthesis
Bridged Bicyclo Compounds / chemistry*
Bridged Bicyclo Compounds / pharmacology
Chelating Agents / chemical synthesis
Chelating Agents / chemistry*
Chelating Agents / pharmacology
Drug Design
HIV Integrase / chemistry*
HIV Integrase / metabolism
HIV Integrase Inhibitors / chemical synthesis
HIV Integrase Inhibitors / chemistry*
HIV Integrase Inhibitors / pharmacology
HIV-1 / drug effects
Humans
Metals / chemistry*
Structure-Activity Relationship

Substances

Azoles
Bridged Bicyclo Compounds
Chelating Agents
HIV Integrase Inhibitors
Metals
HIV Integrase
p31 integrase protein, Human immunodeficiency virus 1