title: Structure-activity relationships of heteroaromatic esters as human rhinovirus 3C protease inhibitors.
abstract: Human rhinovirus 3C protease (HRV 3C(pro)) is known to be a promising target for development of therapeutic agents against the common cold because of the importance of the protease in viral replication as well as its expression in a large number of serotypes. To explore non-peptidic inhibitors of HRV 3C(pro), a series of novel heteroaromatic esters was synthesized and evaluated for inhibitory activity against HRV 3C(pro), to determine the structure-activity relationships. The most potent inhibitor, 7, with a 5-bromopyridinyl group, had an IC(50) value of 80nM. In addition, the binding mode of a novel analog, 19, with the 4-hydroxyquinolinone moiety, was explored by molecular docking, suggesting a new interaction in the S1 pocket.
authors.affiliation: Research Center for Biomolecular Nanotechnology, Department of Life Science, Gwangju Institute of Science and Technology, Republic of Korea.
authors.forename: Isak
authors.initials: I
authors.lastname: Im
authors.forename: Eui Seung
authors.initials: ES
authors.lastname: Lee
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Choi
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012229:Rhinovirus / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D005663:Furans; D011725:Pyridines; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases