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Pyrazole-based cathepsin S inhibitors with improved cellular potency.

Abstract：

:High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of CatS inhibitors. Although substitutions on this heterocyclic framework had a moderate impact on enzymatic potency, dramatic effects on cellular activity were observed. Optimization afforded indole- and benzothiophene-derived analogues that were high affinity CatS inhibitors (IC(50)=20-40 nM) with good cellular potency (IC(50)=30-340 nM).

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wei J,Pio BA,Cai H,Meduna SP,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

doi

10.1016/j.bmcl.2007.08.038

subject

Has Abstract

pub_date

2007-10-15 00:00:00

pages

5525-8

issue

20

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)00983-3

journal_volume

17

pub_type

杂志文章

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