Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase.

Abstract Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 ( 1 ) and the more rigid indazole constraint of MK-6186 ( 2 ). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI’s.