From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety.
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.
Petrocchi
Alessia
A
Department of Medicinal Chemistry and Drug Metabolism, IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy. alessia_petrocchi@merck.com
Koch
Uwe
U
Matassa
Victor G
VG
Pacini
Barbara
B
Stillmock
Kara A
KA
Summa
Vincenzo
V
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D016174:Hepacivirus / Q000201:enzymology; D007202:Indicators and Reagents; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012324:RNA-Dependent RNA Polymerase
D000577:Amides; D019428:HIV Integrase Inhibitors; D007202:Indicators and Reagents; D011743:Pyrimidines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase