Author/Authors :
Jianmei Wei، نويسنده , , Barbara A. Pio، نويسنده , , Hui Cai، نويسنده , , Steven P. Meduna، نويسنده , , Siquan Sun، نويسنده , , Yin Gu، نويسنده , , Wen Jiang، نويسنده , , Robin L. Thurmond، نويسنده , , Lars Karlsson، نويسنده , , James P. Edwards، نويسنده ,
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 (IC50 = 20–40 nM) with good cellular potency (IC50 = 30–340 nM).
