Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers.

doi:10.1016/j.bmcl.2012.09.061

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Article

Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers.

Bioorganic & medicinal chemistry letters - 1 Dec 2012

Rudd Michael T, McIntyre Charles J, Romano Joseph J, Butcher John W, Holloway M Katharine, Bush Kimberly, Nguyen Kevin T, Gilbert Kevin F, Lyle Terry A, Liverton Nigel J, Wan Bang-Lin, Summa Vincenzo, Harper Steven, Rowley Michael, Vacca Joseph P, Carroll Steven S, Burlein Christine, DiMuzio Jillian M, Gates Adam, Graham Donald J, Huang Qian, Ludmerer Steven W, McClain Stephanie, McHale Carolyn, Stahlhut Mark, Fandozzi Christine, Taylor Anne, Trainor Nicole, Olsen David B, McCauley John A

Abstract excerpt

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 R155K, A156T, A156V, and D168V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where ~20-fold improvements in potency are achieved by introduction of...

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PMID: 23084906
DOI: 10.1016/j.bmcl.2012.09.061

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

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