Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors. Part 2: Modification of P3, P4, and P5 regions
| Autor: | John J. M. Wiener, Siquan Sun, Alvah T. Wickboldt, James P. Edwards, Todd K. Jones, Danielle K. Wiener, Lars Karlsson, Alice Lee-Dutra, Steven Nguyen, Cheryl A. Grice |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
chemistry.chemical_classification
Stereochemistry Oxamide Organic Chemistry Clinical Biochemistry Pharmaceutical Science Pyrazole Sulfides Biochemistry Cathepsins Sulfonamide Cell Line chemistry.chemical_compound Structure-Activity Relationship chemistry Thioether Drug Discovery Molecular Medicine Moiety Humans Pyrazoles Protease Inhibitors Molecular Biology Cathepsin S |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(7) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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