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Bioorg Med Chem Lett. 2013 Feb 15;23(4):1070-4. doi: 10.1016/j.bmcl.2012.12.014. Epub 2012 Dec 21.

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

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  • 1Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.


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.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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