Design of a series of bicyclic HIV-1 integrase inhibitors. Part 1: selection of the scaffold

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

doi:10.1016/j.bmcl.2010.07.079

Design of a series of bicyclic HIV-1 integrase inhibitors. Part 1: selection of the scaffold

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5913-7. doi: 10.1016/j.bmcl.2010.07.079. Epub 2010 Jul 27.

Authors

Eric D Jones¹, Nick Vandegraaff, Giang Le, Neil Choi, William Issa, Katherine Macfarlane, Neeranat Thienthong, Lisa J Winfield, Jonathan A V Coates, Long Lu, Xinming Li, Xiao Feng, Changjiang Yu, David I Rhodes, John J Deadman

Affiliation

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

PMID: 20727748
DOI: 10.1016/j.bmcl.2010.07.079

Abstract

HIV integrase inhibitors based on a novel bicyclic pyrimidinone core is presented. Nine variations of the core scaffold are evaluated leading to optimization of the 6:6 core giving compound 48 with an EC(50) of 3 nM against wild type HIV infected T-cells.

MeSH terms

Bridged Bicyclo Compounds / chemical synthesis
Bridged Bicyclo Compounds / chemistry*
Bridged Bicyclo Compounds / 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
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Structure-Activity Relationship
T-Lymphocytes / virology

Substances

Bridged Bicyclo Compounds
HIV Integrase Inhibitors
Pyridines
Pyrimidines
HIV Integrase
p31 integrase protein, Human immunodeficiency virus 1