Peptidomimetic 2-cyanopyrrolidines as potent selective cathepsin L inhibitors

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DOIResolve DOI: http://doi.org/10.1080/14756360701504842
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TypeArticle
Journal titleJournal Of Enzyme Inhibition And Medicinal Chemistry
Volume23
Issue2
Pages190197; # of pages: 8
Subjectactivity; Cathepsin B; cathepsin L; inhibitors; Nitriles; pha; selectivity
AbstractCathepsins have been found to have important physiological roles. The implication of cathepsin L in various types of cancers is well established. In a search for selective cathepsin L inhibitors as anticancer agents, a series of 2-cyanoprrolidine peptidomimetics, carrying a nitrile group as warhead, were designed. Two series of compounds, one with a benzyl moiety and a second with an isobutyl moiety at P(2) position of the enzyme were synthesized. The synthesized compounds were evaluated for inhibitory activity against human cathepsin L and cathepsin B. Although, none of the compounds showed promising inhibitory activity, (E)N-{(S)1-[(S)2-cyano-1-pyrrolidinecarbonyl]-3-methylbutyl}-2,3-diphenylacrylamide (24) with an isobutyl moiety at P(2) was found to show selectivity as a cathepsin L inhibitor (Ki 5.3 muM for cathepsin L and Ki > 100 muM for cathepsin B). This compound could act as a new lead for the further development of improved inhibitors within this inhibitor type.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedNo
NRC number49566
NPARC number3538958
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Record identifiere3a63763-05b0-491b-8116-d83e27afba0f
Record created2009-03-01
Record modified2016-05-09
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