105020-39-1Relevant articles and documents
Discovery of hepatitis C Virus NS3-4A protease inhibitors with improved barrier to resistance and favorable liver distribution
Moreau, Benoi?t,O'Meara, Jeff A.,Bordeleau, Josée,Garneau, Michel,Godbout, Cedrickx,Gorys, Vida,Leblanc, Mélissa,Villemure, Elisia,White, Peter W.,Llinàs-Brunet, Montse
supporting information, p. 1770 - 1776 (2014/04/03)
Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly improved potency against the key resistant variants and with increased liver partitioning.
HEPATITIS C INHIBITOR COMPOUNDS
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Page/Page column 49, (2011/06/23)
Compounds of Formula (I) wherein R1, R2, R3, R4 and R5 are defined herein, maintain good activity against NS3 proteases containing clinically relevant genotype 1a R155K and genotype 1b D168V resistance mutations. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.
NOVEL HERBICIDES
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Page/Page column 110, (2008/06/13)
Compounds of formula I: wherein R1, R2, R3, R4, m, R5, R6, n and Y are as defined in claim 1; or N-oxides, salts and optical isomers thereof. Furthermore, the present invention relates to processes for preparing compounds of formula (I), to herbicidal compositions comprising them and to methods of using them to control plants or to inhibit plant growth.