| Title: | Irreversible Inhibitors of Cysteine Proteases | ||
| Patent/Patent Application Number: | WO 2012/140500 A1 | Publication Date: | October 18, 2012 |
| Priority Application: | Priority Date: | April 15, 2011 | |
| Inventors: | Ahlfors, J. E.; Mekoular, K. | ||
| Assignee Company: | New World Laboratories Inc., Canada | ||
| Disease Area: | Neurodegenerative disease, stroke, spinal cord injury, cancer, myocardial infarction | Biological Target: | Cystein proteases, caspases |
| Summary: | The patent application claims modified peptides/peptide mimetics as selective and irreversible inhibitors of cyteine proteases and caspases for the treatment of a variety of diseases. Compounds of the invention are composed of 1–5 natural or non-natural amino acids and electrophilic “war head” moieties. | ||
| Important Compound Classes: |  |
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| Definitions: | Px, P5, P4, P3, and P2 are natural or non-natural amino acids. | ||
| n is 0–3. | |||
| W is H, alkyl, OH, OR9, CN, NH2, NHR9, NHSOR9, halogen, COR4, COR9, CN, OCOR9, OCO2R9, NO, NO2, NR7R8, NHSO2R9, NHCOR9, SO2R9, or SR9. | |||
| Key Structures: |  |
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| Biological Assays: | Caspase 1–10 inhibitor screening assay. Enzymatic assay using commercially available caspase inhibitor drug screening kits. IC50 values for 31 compounds tested against caspases 1–10 are described. | ||
| Pharmacological Data: | Enzymatic screening assay: | ||
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| Synthesis: | The synthesis of 162 compounds is exemplified. | ||
The authors declare no competing financial interest.