Development of 2-t butyl-N-methyl pyrimidones as potent inhibitors of HIV integrase

M Emilia Di Francesco; Paola Pace; Fabrizio Fiore; Francesca Naimo; Fabio Bonelli; Michael Rowley; Vincenzo Summa

doi:10.1016/j.bmcl.2008.03.017

Development of 2-t butyl-N-methyl pyrimidones as potent inhibitors of HIV integrase

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2709-13. doi: 10.1016/j.bmcl.2008.03.017. Epub 2008 Mar 10.

Authors

M Emilia Di Francesco¹, Paola Pace, Fabrizio Fiore, Francesca Naimo, Fabio Bonelli, Michael Rowley, Vincenzo Summa

Affiliation

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

PMID: 18362069
DOI: 10.1016/j.bmcl.2008.03.017

Abstract

A series of novel 2-(t)butyl-N-methyl pyrimidone HIV-1 integrase inhibitors have been identified. Optimization of the initial lead resulted in compounds such as 9d and 14a, which showed high levels of activity in cell culture inhibiting viral replication with CIC(95) of 10nM in the presence of 50% normal human serum.

MeSH terms

Amides / chemistry
Animals
Cell Survival / drug effects
Cells, Cultured
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / chemistry
HIV Integrase Inhibitors / pharmacology*
Humans
Methylation
Molecular Structure
Pyrimidinones / chemical synthesis*
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship

Substances

Amides
HIV Integrase Inhibitors
Pyrimidinones