Development of 2-t butyl-N-methyl pyrimidones as potent inhibitors of HIV integrase.
A series of novel 2-(t)butyl-N-methyl pyrimidone HIV-1 integrase inhibitors have been identified. Optimization of the initial lead resulted in compounds such as 9d and 14a, which showed high levels of activity in cell culture inhibiting viral replication with CIC(95) of 10nM in the presence of 50% normal human serum.
Di Francesco
M Emilia
ME
Department of Medicinal Chemistry, IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy. mariaemilia_difrancesco@merck.com
Pace
Paola
P
Fiore
Fabrizio
F
Naimo
Francesca
F
Bonelli
Fabio
F
Rowley
Michael
M
Summa
Vincenzo
V
D000577:Amides / Q000737:chemistry; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000577:Amides; D019428:HIV Integrase Inhibitors; D011744:Pyrimidinones