Synthesis and antiviral evaluation of a novel series of homoserine-based inhibitors of the hepatitis C virus NS3/4A serine protease. Issue 18 (15th September 2015)

• Record Type: Journal Article
• Authors: Alexandre, François-René; Brandt, Guillaume; Caillet, Catherine; Chaves, Dominique; Convard, Thierry; Derock, Michel; Gloux, Damien; Griffon, Yann; Lallos, Lisa; Leroy, Frédéric; Liuzzi, Michel; Loi, Anna-Giulia; Moulat, Laure; Musiu, Chiara; Parsy, Christophe; Rahali, Houcine; Roques, Virginie; Seifer, Maria; Standring, David; Surleraux, Dominique
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 18(2015)
• Page Start: 3984
• Page End: 3991
• Publication Date: 2015-09-15
• Subjects: Hepatitis C -- HCV NS3/4A protease inhibitors -- Macrocycle -- Synthesis and biological evaluation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.07.020
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We disclose here the synthesis of a series of macrocyclic HCV protease inhibitors, where the homoserine linked together the quinoline P2′ motif and the macrocyclic moiety. These compounds exhibit potent inhibitory activity against HCV NS3/4A protease and replicon cell based assay. Their enzymatic and antiviral activities are modulated by substitutions on the quinoline P2′ at position 8 by methyl and halogens and by small heterocycles at position 2. The in vitro structure activity relationship (SAR) studies and in vivo pharmacokinetic (PK) evaluations of selected compounds are described herein.