From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety

Alessia Petrocchi; Uwe Koch; Victor G Matassa; Barbara Pacini; Kara A Stillmock; Vincenzo Summa

doi:10.1016/j.bmcl.2006.10.054

From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety

Bioorg Med Chem Lett. 2007 Jan 15;17(2):350-3. doi: 10.1016/j.bmcl.2006.10.054. Epub 2006 Oct 25.

Authors

Alessia Petrocchi¹, Uwe Koch, Victor G Matassa, Barbara Pacini, Kara A Stillmock, Vincenzo Summa

Affiliation

¹ Department of Medicinal Chemistry and Drug Metabolism, IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy. alessia_petrocchi@merck.com

PMID: 17107799
DOI: 10.1016/j.bmcl.2006.10.054

Abstract

4,5-Dihyroxypyrimidine carboxamides, which evolved from a related series of HCV NS5b polymerase inhibitors, have been optimized to provide selective HIV integrase strand transfer inhibitors. Extensive SAR around the benzylamide moiety led to the identification of the p-fluorobenzylamide as optimal in the enzymatic assay.

Publication types

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

MeSH terms

Amides / chemical synthesis
Amides / pharmacology
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / pharmacology*
Hepacivirus / enzymology
Indicators and Reagents
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors

Substances

Amides
HIV Integrase Inhibitors
Indicators and Reagents
Pyrimidines
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus