2 results match your criteria pyrazole-based thioethers

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Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors. Part 2: Modification of P3, P4, and P5 regions.

Bioorg Med Chem Lett 2010 Apr 1;20(7):2375-8. Epub 2010 Feb 1.

Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.

A novel class of tetrahydropyrido-pyrazole thioether amines that display potency against human Cathepsin S have been previously reported. Here, further SAR investigations of the P3, P4, and P5 regions are described. In particular, 4-fluoropiperidine is identified as a competent P3 binding element when utilized in conjunction with a (S)-2-hydroxypropyl linker-containing P5 moiety and oxamide or sulfonamide P4 substitution. Read More

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Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors: part 1.

Bioorg Med Chem Lett 2010 Apr 28;20(7):2370-4. Epub 2010 Jan 28.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.

A series of pyrazole-based thioethers were prepared and found to be potent cathepsin S inhibitors. A crystal structure of 13 suggests that the thioether moiety may bind to the S3 pocket of the enzyme. Additional optimization led to the discovery of aminoethylthioethers with improved enzymatic activity and submicromolar cellular potency. Read More

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