4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species

• DOI: 10.1021/jm060854f
• Publication Date: 2006-10-25T10:51:08Z
• Authors: Vincenzo Summa; Alessia Petrocchi; Victor G. Matassa; Cristina Gardelli; Ester Muraglia; Michael Rowley; Odalys Gonzalez Paz; Ralph Laufer; Edith Monteagudo; Paola Pace
• Keywords: Carboxamide; Integrase inhibitor

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. optimization of physicochemical properties, pharmacokinetic profiles, potency led to the identification 13 in series 18 N-methylpyrimidinone having low nanomolar activity cellular spread assay presence 50% normal human serum very good pharmacokinetics preclinical species.