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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Development of potent macrocyclic inhibitors of genotype 3a HCV NS3/4A protease
Michael T Rudd1, John A McCauley, Joseph J Romano
1Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. michael_rudd@merck.com
Bioorganic & Medicinal Chemistry Letters
|October 2, 2012
Abstract:
A series of macrocyclic compounds containing 2-substituted-quinoline moieties have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K mutant activity while maintaining the high rat liver exposure. Cyclization of the 2-substituted quinoline substituent led to a series of tricyclic P2 compounds which also display superb gt3a potency.

