Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant

Ester Muraglia; Olaf D Kinzel; Ralph Laufer; Michael D Miller; Gregory Moyer; Vandna Munshi; Federica Orvieto; Maria Cecilia Palumbi; Giovanna Pescatore; Michael Rowley; Peter D Williams; Vincenzo Summa

doi:10.1016/j.bmcl.2006.02.024

Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant

Bioorg Med Chem Lett. 2006 May 15;16(10):2748-52. doi: 10.1016/j.bmcl.2006.02.024. Epub 2006 Feb 28.

Authors

Ester Muraglia¹, Olaf D Kinzel, Ralph Laufer, Michael D Miller, Gregory Moyer, Vandna Munshi, Federica Orvieto, Maria Cecilia Palumbi, Giovanna Pescatore, Michael Rowley, Peter D Williams, Vincenzo Summa

Affiliation

¹ Department of Medicinal Chemistry, IRBM/MRL Rome, Via Pontina Km 30,600, 00040 Pomezia, Rome, Italy. Ester_Muraglia@merck.com

PMID: 16503141
DOI: 10.1016/j.bmcl.2006.02.024

Abstract

A series of aryltetrazolylacetanilides was synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors on wild-type virus and on the clinically relevant K103N mutant strain. Extensive SAR investigation led to potent compounds, with nanomolar activity on K103N, and orally bioavailable in rats.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetanilides / chemistry
Acetanilides / pharmacology*
Animals
HIV Reverse Transcriptase / antagonists & inhibitors*
HIV-1 / drug effects*
HIV-1 / enzymology
HIV-1 / genetics
Mutation*
Rats
Reverse Transcriptase Inhibitors / chemistry
Reverse Transcriptase Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Acetanilides
Reverse Transcriptase Inhibitors
HIV Reverse Transcriptase
thioacetanilide