Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors. Issue 5 (1st March 2018)

• Record Type: Journal Article
• Authors: Namoto, Kenji; Sirockin, Finton; Sellner, Holger; Wiesmann, Christian; Villard, Frederic; Moreau, Robert J.; Valeur, Eric; Paulding, Stephanie C.; Schleeger, Simone; Schipp, Kathrin; Loup, Joachim; Andrews, Lori; Swale, Ryann; Robinson, Michael; Farady, Christopher J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 5(2018)
• Page Start: 906
• Page End: 909
• Publication Date: 2018-03-01
• Subjects: Rhinovirus 3C protease -- Protease inhibition -- Covalent inhibitor -- Macrocycle -- Structure-based drug design -- Solid phase synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.01.064
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor10 with sub-micromolar antiviral activity.