Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P2'-ligands

Arun K Ghosh; Gary Schiltz; Ramu Sridhar Perali; Sofiya Leshchenko; Stephanie Kay; D Eric Walters; Yasuhiro Koh; Kenji Maeda; Hiroaki Mitsuya

doi:10.1016/j.bmcl.2006.01.011

Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P2'-ligands

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1869-73. doi: 10.1016/j.bmcl.2006.01.011. Epub 2006 Feb 15.

Authors

Arun K Ghosh¹, Gary Schiltz, Ramu Sridhar Perali, Sofiya Leshchenko, Stephanie Kay, D Eric Walters, Yasuhiro Koh, Kenji Maeda, Hiroaki Mitsuya

Affiliation

¹ Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu

PMID: 16480871
DOI: 10.1016/j.bmcl.2006.01.011

Abstract

A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Cell Line
Crystallography, X-Ray
Drug Design
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry*
HIV Protease Inhibitors / pharmacology
HIV-1 / drug effects*
Indoles / chemistry*
Ligands
Models, Molecular

Substances

HIV Protease Inhibitors
Indoles
Ligands

Grants and funding

GM 53386/GM/NIGMS NIH HHS/United States