Development of 2-pyrrolidinyl-N-methyl pyrimidones as potent and orally bioavailable HIV integrase inhibitors

Marco Ferrara; Fabrizio Fiore; Vincenzo Summa; Cristina Gardelli

doi:10.1016/j.bmcl.2010.07.042

Development of 2-pyrrolidinyl-N-methyl pyrimidones as potent and orally bioavailable HIV integrase inhibitors

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5031-4. doi: 10.1016/j.bmcl.2010.07.042. Epub 2010 Jul 15.

Authors

Marco Ferrara¹, Fabrizio Fiore, Vincenzo Summa, Cristina Gardelli

Affiliation

¹ Department of Medicinal Chemistry IRBM-MRL, Pomezia (RM), Italy. [email protected]

PMID: 20674351
DOI: 10.1016/j.bmcl.2010.07.042

Abstract

A series of 2-pyrrolidinyl-N-methyl pyrimidones HIV integrase inhibitors has been explored leading to the identification of derivative 13, which showed high activity at inhibiting viral replication in cell culture, favorable pharmacokinetic profile in two preclinical species, and an attractive profile against a panel of HIV-integrase mutants.

MeSH terms

Administration, Oral
Animals
Biological Availability
HIV Integrase Inhibitors / administration & dosage
HIV Integrase Inhibitors / pharmacokinetics
HIV Integrase Inhibitors / pharmacology*
Pyrimidinones / administration & dosage
Pyrimidinones / pharmacokinetics
Pyrimidinones / pharmacology*
Rats

Substances

HIV Integrase Inhibitors
Pyrimidinones