ABSTRACT
Discovery efforts were focused on identifying a non-nucleoside antiviral for treating infections caused by human cytomegalovirus (HCMV) with equal or better potency and diminished toxicity compared to current therapeutics. This Letter describes the HCMV DNA polymerase inhibition and in vitro antiviral activity of various 2-aryl-2-hydroxy ethylamine substituted 1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamides.
Subject(s)
Antiviral Agents/chemistry , Protease Inhibitors/chemistry , Quinoxalines/chemistry , Serine Endopeptidases/drug effects , Antiviral Agents/pharmacology , Drug Design , Protease Inhibitors/pharmacology , Quinoxalines/pharmacologyABSTRACT
PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.
