title: From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry and Drug Metabolism, IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy. alessia_petrocchi@merck.com
authors.forename: Alessia
authors.initials: A
authors.lastname: Petrocchi
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Victor G
authors.initials: VG
authors.lastname: Matassa
authors.forename: Barbara
authors.initials: B
authors.lastname: Pacini
authors.forename: Kara A
authors.initials: KA
authors.lastname: Stillmock
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Summa
mesh_terms: 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
chemical_list: 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