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Updated: May 27, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase
Robert Gomez1, Samson Jolly, Theresa Williams
1Department of West Point Discovery Chemistry, Merck Research Labs., 770 Sumneytown Pike, PO Box 4, West Point, PA 19486-0004, USA. Robert_gomez@merck.com
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.
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