Peptide analogs as irreversible interleukin-1.beta. protease inh

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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514 17, 514 18, 530330, 530331, 562571, A61K 3805

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active

059858389

ABSTRACT:
Disclosed are compounds, compositions and methods for inhi.beta.iting interleukin-1.beta. protease activity, the compounds .alpha.-substituted methyl ketones having the formula (I) set forth herein. These compounds are inhibitors of IL-1.beta. converting enzyme and as such are useful as therapeutic agents for certain infectious diseases.

REFERENCES:
patent: 5055451 (1991-10-01), Krantz et al.
patent: 5374623 (1994-12-01), Zimmerman
patent: 5430128 (1995-07-01), Chapman
Dolle, R.E., et al. "P1 Aspartate-Based Peptide alpha-((2,6-Dichlorobenzoyl) oxy) methyl Ketones as Potent Time Dependent Inhibitors of Interleukin-1beta-Converting Enzyme," J. Med. Chem. 37, pp. 563-564 (1994).
Thornberry, N.A., et al. "Inactivation of Interleukin-1beta Converting Enzyme by Peptide (Acyloxy)methyl Ketones," Biochemistry 33, pp. 3934-3940 (1994).
Sleath, P.R. et al. "Substrate Specificity of the Protease That Processes Human Interleukin-1beta," J. Biol. Chem. 24, pp. 14526-14528 (1990).
Thornberry, N.A., et al. "A Novel Heterodimeric Cysteine Protease is Required for Interleukin-1beta Processing in Monocytes," Nature 356, pp. 768-774 (1992).
Krantz, A., et al. "Peptidyl (Acyloxy) methyl Ketones and the Quiescent Affinity Label Concept: The Departing Group as a Variable Structural Element in the Design of Inactivators of Cysteine Proteinases," Biochemistry 30, pp. 4678-4687 (1991).

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