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ID: ALA1137473

Journal: Bioorg Med Chem Lett

Title: Pyrazole-based cathepsin S inhibitors with improved cellular potency.

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

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).

CiteXplore: 17822900

DOI: 10.1016/j.bmcl.2007.08.038