Pyrazole-based arylalkyne cathepsin S inhibitors. Part III: modification of P4 region.

Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described.

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