Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594407 | Bioorganic & Medicinal Chemistry Letters | 2012 | 7 Pages |
Abstract
A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155Â K, A156T, A156Â V, and D168Â V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where â¼20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Michael T. Rudd, Charles J. McIntyre, Joseph J. Romano, John W. Butcher, M. Katharine Holloway, Kimberly Bush, Kevin T. Nguyen, Kevin F. Gilbert, Terry A. Lyle, Nigel J. Liverton, Bang-Lin Wan, Vincenzo Summa, Steven Harper, Michael Rowley,