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.
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.
Petrocchi
Alessia
A
Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL, Via Pontina, Km 30.600, 00040 Pomezia (RM), Italy. alessia_petrocchi@merck.com
Jones
Philip
P
Rowley
Michael
M
Fiore
Fabrizio
F
Summa
Vincenzo
V
D000818:Animals; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D019428:HIV Integrase Inhibitors; D011719:Pyrazines; D011743:Pyrimidines; D009584:Nitrogen