Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-03-17
1997-08-12
Grumbling, Matthew V.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514 80, 514211, 514214, 540500, 540501, 540502, 540503, 540521, 540523, 540579, 540593, 546112, 549 28, 549366, C07D25504, C07D24310
Patent
active
056566271
ABSTRACT:
The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.
REFERENCES:
patent: 4276298 (1981-06-01), Jones et al.
patent: 4369183 (1983-01-01), Jones et al.
patent: 4499295 (1985-02-01), Mueller et al.
patent: 4551279 (1985-11-01), Mueller et al.
patent: 4584397 (1986-04-01), Mueller et al.
patent: 4968607 (1990-11-01), Dower et al.
patent: 5008245 (1991-04-01), Digenis et al.
patent: 5055451 (1991-10-01), Krantz et al.
patent: 5081228 (1992-01-01), Dower et al.
patent: 5158936 (1992-10-01), Krantz et al.
patent: 5180812 (1993-01-01), Dower et al.
patent: 5374623 (1994-12-01), Zimmerman et al.
patent: 5411985 (1995-05-01), Bills et al.
patent: 5416013 (1995-05-01), Black et al.
patent: 5430128 (1995-07-01), Chapman et al.
patent: 5434248 (1995-07-01), Chapman et al.
patent: 5462939 (1995-10-01), Dolle et al.
patent: 5486623 (1996-01-01), Zimmerman et al.
patent: 5498616 (1996-03-01), Mallomo et al.
patent: 5498695 (1996-03-01), Daumy et al.
patent: 5552400 (1996-09-01), Dolle et al.
P. Sleath et al., "Substrate Specificity of the Protease that Processes Human Interleukin-1.beta.", J. Biol. Chem., 265, pp. 14526-14528 (1990).
R. Taylor & O. Kennard, "Hydrogen-Bond Geometry in Organic Crystals", Acc. Chem. Res., 17, pp. 320-326 (1984).
C. Thornber, "Isosterism and Molecular Modification in Drug Design", Chem. Soc. Rev., 8, pp. 563-580 (1979).
N. Thornberry et al., "A Novel Heterodimeric Cysteine Protease is Required for Interleukin-1.beta. Processing in Monocytes", Nature, 356, pp. 768-774 (1992).
N. Thornberry et al., "Inactivation of Interleukin-1.beta. Converting Enzyme by Peptide (Acyloxy)methyl Ketones", Biochemistry, 33, pp. 3934-3940 (1994).
J. Travis, "Proteins and Organic Solvents Make an Eye-Opening Mix", Science, 262, p. 1374 (1993).
J. Uhl et al., "Secretion of Human Monocyte Mature IL-1.beta.: Optimization of Culture Conditions and Inhibition by ICE Inhibitors", Inflammation Research Association (7th Internat. Conf.), W41 (1994).
N.P.C. Walker et al., "Crystal Structure of the Cysteine Protease Interleukin-1-.beta.-Converting Enzyme: A(p20/p10).sub.2 Homodimer", Cell, 78, pp. 343-352 (1994).
P. Warner, et al., "Pyridone HLE Inhibitors: Variation of the 3 and 5 Substituents", Royal Soc. Chem. Abs. (7th RSC-SCI Med. Chem. Symp.), p.23 (1993).
S. Weiner et al., "A New Force Field for Molecular Mechanical Simulation of Nucleic Acids and Proteins", J. Am. Chem. Soc., 106, pp. 765-784 (1984).
K.P. Wilson et al., "Structure and Mechanism of Interleukin-1.beta. Converting Enzyme", Nature, 370, pp. 270-275 (1994).
C. Wong & J. McCammon, "Dynamics and Design of Enzymes and Inhibitors", J. Am. Chem. Soc., 108, pp. 3830-3832 (1986).
P. Wooley et al., "The Effect of an Interleukin-1 Receptor Antagonist Protein on Type II Collagen-induced Arthritis and Antigen-induced Arthritis in Mice", Arthritis Rheum., 36, pp. 1305-1314 (1993).
J. Yuan et al., "The C.elegans Cell Death Gene ced-3 Encodes a Protein Similar to Mammalian Interleukin-1.beta.-Converting Enzyme", Cell, 75, pp. 641-652 (1993).
D. Alberg & S. Schreiber, "Structure-Based Design of a Cyclophilin-Calcineurin Bridging Ligand", Science, 262, pp. 248-250 (1993).
P. Andrews, "Functional Groups, Drug-Receptor Interactions and Drug Design", Trends Pharmacol. Sci., 7, pp. 148-151 (1986).
K. Appelt et al., "Design of Enzyme Inhibitors Using Iterative Protein Crystallographic Analysis", J. Med. Chem., 34, pp. 1925-1934 (1991).
M. Ator, "Peptide and Non-peptide Inhibitors of Interleukin-1.beta. Converting Enzyme", Cambridge Healthtech Institute (Inflammatory Cytokine Antagonists Targets, Strategies, and Indication), (1994).
E. Baker & J. Drenth, "The Thiol Proteases: Structure and Mechanism", in Biological Macromolecules and Assemblies, 3, pp. 313-368 (F. Jurnak & A. McPherson eds., 1987).
J. Baldwin et al., "Thienothiopyran-2-sulfonamides: Novel Topically Active Carbonic Anhydrase Inhibitors for the Treatment of Glaucoma", J. Med. Chem., 32, pp. 2510-2513 (1989).
M.Barinaga, "Death Gives Birth to the Nervous System. But How?", Science, 259, pp. 762-763 (1993).
P. Bartlett et al., "CAVEAT: A Program to Facilitate the Structure-derived Design of Biologically Active Molecules", Molecular Recognition: Chemical and Biochemical Problems, 78, pp. 182-196 (1989).
P. Bender & J. Lee, "Pharmacological Modulation of Interleukin-1", Annu. Rep. Med. Chem., 25, pp. 185-193 (1989).
R. Black et al., "Activation of Interleukin-1.beta. by a Co-induced Protease", FEBS Lett, 247, pp. 386-390 (1989).
H. Bohm, "The Computer Program LUDI: A New Method for the De Novo Design of Enzyme Inhibitors", J. Comput. Aided Mol. Des., 6, pp. 61-78 (1992).
J. Breitner et al., "Inverse Association of Anti-inflammatory Treatments and Alzheimer's Disease: Initial Results of a Co-twin Control Study", Neurology, 44, pp. 227-232 (1994).
B. Brooks et al., "Charmm: A Program for Macromolecular Energy, Minimization, and Dynamics Calculations", J. Comput. Chem., 4, pp. 187-217 (1983).
A. Brunger, "Extension of Molecular Replacement: A New Search Strategy Based on Patterson Correlation Refinement", Acta Crystallogr. A, 46, pp. 46-57 (1990).
A. Brunger & A. Krukowski, "Slow-Cooling Protocols for Crystallographic Refinement by Simulated Annealing", Acta Crystallogr. A, 46, pp. 585-593 (1990).
U. Burkert & N. Allinger, "Methods for the Computation of Molecular Geometry" in Molecular Mechanics, pp. 59-78 (1982).
M. Carson, "Ribbons 2.0", J. App. Crystallogr., 24, pp. 958-961 (1991).
F. Casano et al., "The Structure and Complete Nucleotide Sequence of the Murine Gene Encoding Interleukin-1.beta. Converting Enzyme (ICE)", Genomics, 20, pp. 474-481 (1994).
D. Cerretti et al., "Molecular Cloning of the Interleukin-1.beta. Converting Enzyme", Science, 256, pp. 97-100 (1992).
K. Chapman, "Synthesis of a Potent, Reversible Inhibitor of Interleukin-1.beta. Converting Enzyme", Bioorg. Med. Chem. Lett., 2, pp. 613-618 (1992).
N. Cohen, "Drug Design in Three Dimensions", Advances in Drug Research, 14, pp. 41-145 (1985).
N. Cohen, "Rational Drug Design and Molecular Modeling", Drugs of the Future, 10, pp. 311-328 (1985).
N. Cohen et al., "Molecular Modeling Software and Methods for Medicinal Chemistry", J. Med. Chem., 33, pp. 883-894 (1990).
D. Davies & D. Segal, "Protein Crystallization: Micro Techniques Involving Vapor Diffusion", Methods Enzymol., 22, pp. 266-269 (1971).
K. Dill, "Dominant Forces in Protein Folding", Biochemistry, 29, pp. 7133-7155 (1990).
C. Dinarello, "Role of Interleukin-1 in Infectious Diseases", Immunol. Rev., 127, pp. 119-146 (1992).
C. Dinarello et al., "Anticytokine Strategies in the Treatment of the Systemic Inflammatory Response Syndrome", J. Am. Med. Assoc., 269, pp. 1829-1835 (1993).
R. Dolle et al., "Aspartyl .alpha.-((1-Phenyl-3-(trifluoromethyl)-pyrazol-5-yl)oxy)methyl Ketones as Interleukin-1.beta. Converting Enzyme Inhibitors. Significance of the P.sub.1 and P.sub.3 Amido Nitrogens for Enzyme-Peptide Inhibitor Binding", J. Med. Chem., 37, pp. 3863-3865 (1994).
R. Dolle et al., "Aspartyl .alpha.-((Diphenylphosphinyl)oxy)methyl Ketones as Novel Inhibitors of Interleukin-1.beta. Converting Enzyme. Utility of the Diphenylphosphinic Acid Leaving Group for the Inhibition of Cysteine Proteases", J. Med. Chem., 38, pp. 220-222 (1995).
R. Dolle et al., "P.sub.1 Aspartate-Based Peptide .alpha.-((2,6-Dichlorobenzoyl)oxy)methyl Ketones as
Bemis Guy W.
Golec Julian M. C.
Lauffer David J.
Livingston David J.
Mullican Michael D.
Dixon Lisa A.
Grumbling Matthew V.
Haley, Jr. James F.
Ngo Tamthom T.
Vertex Pharmaceuticals Inc.
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