N-(4-Fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamides a novel class of potent HIV-1 integrase inhibitors

Alessia Petrocchi; Philip Jones; Michael Rowley; Fabrizio Fiore; Vincenzo Summa

doi:10.1016/j.bmcl.2009.05.098

N-(4-Fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamides a novel class of potent HIV-1 integrase inhibitors

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4245-9. doi: 10.1016/j.bmcl.2009.05.098. Epub 2009 May 29.

Authors

Alessia Petrocchi¹, Philip Jones, Michael Rowley, Fabrizio Fiore, Vincenzo Summa

Affiliation

¹ Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL, Via Pontina, Km 30.600, 00040 Pomezia (RM), Italy. [email protected]

PMID: 19523819
DOI: 10.1016/j.bmcl.2009.05.098

Abstract

A novel class of tetrahydro-pyrazinopyrimidine-2-carboxamides have been identified as HIV-1 integrase inhibitors. Optimization of the initial lead culminated in the discovery of a series of compounds with high potency on the enzyme and an antiviral cell-based activity equivalent to that showed by Raltegravir, the first in class HIV-1 integrase inhibitor.

Publication types

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

MeSH terms

Animals
Cell Line
Chemistry, Pharmaceutical / methods
Drug Design
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy / methods
Models, Chemical
Nitrogen / chemistry
Pyrazines / chemical synthesis*
Pyrazines / pharmacology
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

HIV Integrase Inhibitors
Pyrazines
Pyrimidines
Nitrogen