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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.

SUBMITTER: Im I

PROVIDER: S-EPMC7126291 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Structure-activity relationships of heteroaromatic esters as human rhinovirus 3C protease inhibitors.

Im Isak I Lee Eui Seung ES Choi Soo Jeong SJ Lee Ju-Yeon JY Kim Yong-Chul YC

Bioorganic & medicinal chemistry letters 20090503 13

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 inhibit ...[more]

PMID: 19464175

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