当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies.

Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies.

Abstract：

:The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bind to HRV serotype 14 3CP with inhibition activities (kobs/[I]) ranging from 100 to 600 000 M-1 s-1. These inhibitors are also shown to exhibit antiviral activity when tested against HRV-14-infected H1-HeLa cells with EC50's approaching 0.50 microM. Extensive structure-activity relationships developed by Michael acceptor alteration are reported along with the evaluation of several compounds against HRV serotypes other than 14. A 2.0 A crystal structure of a peptide-derived inhibitor complexed with HRV-2 3CP is also detailed.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Dragovich PS,Webber SE,Babine RE,Fuhrman SA,Patick AK,Matthews DA,Lee CA,Reich SH,Prins TJ,Marakovits JT,Littlefield ES,Zhou R,Tikhe J,Ford CE,Wallace MB,Meador JW 3rd,Ferre RA,Brown EL,Binford SL,Harr JE,DeLisle

doi

10.1021/jm980068d

subject

Has Abstract

pub_date

1998-07-16 00:00:00

pages

2806-18

issue

15

eissn

0022-2623

issn

1520-4804

pii

jm980068d

journal_volume

41

pub_type

杂志文章

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