.beta.-sheet mimetics and use thereof as protease inhibitors

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

514248, 514405, 548356, 562562, A01N 4358

Patent

active

060203315

ABSTRACT:
There are disclosed .beta.-sheet mimetics and methods relating to the same for imparting or stabilizing the .beta.-sheet structure of a peptide, protein or molecule. In one aspect, the .beta.-sheet mimetics are covalently attached at the end or within the length of the peptide or protein. The .beta.-sheet mimetics have utility as protease inhibitors generally, including activity as serine protease inhibitors such as thrombin, elastase and Factor X.

REFERENCES:
patent: 4307094 (1981-12-01), Hassall et al.
Adam et al., "Determination of the Triplet Lifetimes of 1,3-Cyclopentadiyl Biradicals Derived from the Photodenitrogenation of Azoalkanes with Time-Resolved Photoacoustic Calorimetry," J. Org. Chem. 58: 1477-1482, 1993.
Goldschmidt et al., "Activation Of Electron Deficient Cycloheptatrienes By Tricarbonyliron Complexation," Tetrahedron Letters 31(46): 6711-6712, 1990.
Grangier et al., "Reactivity of Nucleophilic Uracil Derivatives," J. Heterocyclic Chem. 31: 1707-1714, 1994.
Robl et al., "Dual Metalloprotease Inhibitors. 6. Incorporation of Bicyclic and Substituted Monocyclic Azepinones as Dipeptide Surrogates in Angiotensin-Converting Enzyme/Neutral Endopeptidase Inhibitors," J. Med. Chem. 39: 494-502, 1996.
Allen et al., "Molecular Modeling of .gamma.-Lactam Analogues Of .beta.-Lactam Antibacterial Agents: Synthesis And Biological Evaluation Of Selected Penem And Carbapenem Analogues," Tetrahedron 45(7): 1905-1928, 1989.
Attwood et al., "The Design and Synthesis of the Angiotensin Converting Enzyme Inhibitor Cilazapril and Related Bicyclic Compounds," Chem. Soc. Perkin Trans. I: 1011-1019, 1986.
Baldwin and Lee, "Synthesis Of Bicyclic .gamma.-Lactams Via Oxazolidinones," Tetrahedron 42(23): 6551-6554, 1986.
Baldwin et al., ".gamma.-Lactam Analogues Of .beta.-Lactam Antibiotics," The Journal of Antibiotics 44(1):1-24, 1991.
Baldwin et al., ".gamma.-Lactam Analogues of Penicillanic and Carbapenicillanic Acids," J. Chem. Soc., Chem. Commun. 5: 250-252, 1983.
Baldwin et al., ".gamma.-Lactam Analogues Of Penicillanic and Carbapenicillanic Acids," Tetrahedron 40(21): 4513-4525, 1984.
Baldwin et al., ".gamma.-Lactam Formation from Tripeptides with Isopenicillin N Synthase," J. Chem. Soc. Commun. (16): 1128-1130, 1988.
Baldwin et al., "A .gamma.-Lactam Analogue Of Penems Possessing Antibacterial Activity," Tetrahedron Letters 27(30):3461-3464, 1986.
Baldwin et al., "A .gamma.-Lactam Analogue Of The Penems Possessing Antibacterial Activity," Tetrahedron 45(14): 4537-4550, 1989.
Baldwin et al., "Synthesis Of A Bicyclic .gamma.-Lactam Dipeptide Analogue," Heterocycles 34(5): 903-906, 1992.
Baldwin et al., "Synthesis Of A Novel Bicyclic .gamma.-Lactam Analogue Of The 1-Oxapenams," Tetrahedron 30(30): 4019-4020, 1989.
Baldwin et al., "Synthesis of Potential .beta.-Turn Bicyclic Dipeptide Mimetics," J. Chem. Soc., Chem. Commun. (11): 935-936, 1993.
Bauer et al., "Mehrfach ungesattigte Radikalkationen: Regio- und Stereochemie der oxidativen Dimerisierung von Heptafulvenen," Chem. Ber. 117: 809-826, 1984.
Baydar et al., "Acyl Analogues of the Ene Reaction," J. Chem. Soc. Chem. Comm. pp. 650-652, 1976.
Belshaw et al., "Synthesis, Structure and Mechanism in Immunophilin Research," Synlett: 381-392, 1994.
Bernabeu et al., "(2E)-4-Methoxy-2,4-pentadienamides as New Dienes in the Diels-Alder Reaction," Tetrahedron Letters 37(20): 3595-3598, 1996.
Boyd et al., ".gamma.-Lactam Analogues Of Carbapenems," Tetrahedron Letters 27(30): 3457-3460, 1986.
Boyd et al., ".gamma.-Lactam Analogues Of The Penems," Tetrahedron Letters 27(30): 3453-3456, 1986.
Boyd et al., "The Chemistry of N-Substituted 3-Amino-1H-2-benzopyran-1-ones and 5-Amino-2,3-dihydrofuran-2-ones. Ene-type Reactions involving Transfer of Acyl Groups. X-Ray Crystal Structure of cis-3,4-Dihydro-4-morpholinocarbonyl-3-p-nitropheynl-1H-2-benzopyran-1-one ," J. Chem Soc. Perkin Trans. 1: pp. 1351-1360, 1978.
Claridge et al., "Synthesis And Analysis Of Leu-Enkephalin Analogues Containing Reverse Turn Peptidomimetics," Biorganic & Medicinal Chemistry Letters 6(4): 485-490, 1996.
Colombo et al., "Conformationally Constrained Dipeptides: Synthesis of 7,5- and 6,5-Fused Bicyclic Lactams by Stereoselective Radical Cyclizations," Tetrahedron Letters 36(4): 625-628, 1995.
Colombo et al., "Synthesis of 7,5-Fused Bicyclic Lactams by Stereoselective Radical Cyclization," Tetrahedron Letters 35(23): 4031-4034, 1994.
Cornille et al., "Anodic Amide Oxidations: Conformationally Restricted Peptide Building Blocks From The Direct Oxidation of Dipeptides," Tetrahedron Letters 35(38): 6989-6992, 1994.
Cornille et al., "Electrochemical Cyclization of Dipeptides toward Novel Bicyclic, Reverse-Turn Peptidomimetics. 1. Synthesis and Conformational Analysis of 7,5-Bicyclic Systems," J. Am. Chem. Soc. 117: 909-917, 1995.
Cowley, "Regio- and Stereo-selective Intermolecular Interceptions of a Conjugated N-Acylhydrazonium Ion," Tetrahedron Letters 35(42): 7853-7856, 1994.
Du Vigneaud and Carpenter, in The Chemistry of Penicillin, Clarke et al. (eds.), Princeton University Press, Princeton, USA, 1949, pp. 1004-1017.
Etzkorn et al., "Cyclic Hexapaptides and Chimeric Peptides as Mimics of Tendamistat," J. Am. Chem. Soc. 116: 10412-10425, 1994.
Fobian et al., "New Routes To Conformationally Restricted Peptide Building Blocks: A Convenient Preparation Of Bicyclic Piperazinone Derivatives," Bioorganic & Medicinal Chemistry Letters 6(3): 315-318, 1996.
Gilbert and Thomas, "Nuclear Magnetic Resonance Studies and Conformations of Bicyclic Inhibitors of Angiotensin-converting Enzyme. Part 1. Octahydropyridazo[1,2-.alpha.]-pyridizanediones as Models for Alanylproline and Captopril," J. Chem. Soc. Perkin Trans. 11(7): 1077-1082, 1985.
Hanessian et al., "Design And Synthesis Of A Prototype Model Antagonist Of Tachykinin NK-2 Receptor," Bioorganic & Medicinal Chemistry Letters 4(11): 1397-1400, 1994.
Hashiguchi et al., "Synthesis of .gamma.-Lactam Analogues of Carbapenems with Substituted-thio Groups at the C-3 Position," J. Chem. Soc. Perkin Trans. I(8): 2345-2532, 1988.
Hassall et al., "The Design and Synthesis of New Triazolo, Pyrazolo-, and Pyridazo-pyridazine Derivatives as Inhibitors of Angiotensin Converting Enzyme," J. Chem. Soc. Perkin Trans. I: 155-164, 1984.
Jungeheim and Sigmund, "1,3-Dipolar Cycloaddition Reactions of Pyrazolidinium Ylides with Acetylenes. Synthesis of a New Class of Antibacterial Agents," J. Org. Chem. 52: 4007-4013, 1987.
Jungheim et al., "1,3-Dipolar Cycloaddition Reactions Of Pyrazolidinium Ylides With Vinyl Sulfones. A Regioselective Synthesis Of Bicyclic Pyrazolidinone Antibacterial Agents," Tetrahedron 44(11): 3119-3126, 1988.
Jungheim et al., "Bicyclic Pyrazolidinones, A New Class Of Antibacterial Agent Based On The .beta.-Lactam Model," Tetrahedron Letters 28(3): 285-288, 1987.
Jungheim et al., "Bicyclic Pyrazolidinones, Steric And Electronic Effects On Antibacterial Activity," Tetrahedron Letters 28(3): 289-292, 1987.
Li et al., "Conformationally Restricted Peptide Mimetics: The Incorporation of 6,5-Bicyclic Lactam Ring Skeletons into Peptides," J. Org. Chem. 60: 8155-8170, 1995.
Lombart and Lubell, "A Claisen condensation approach to prepare azabicycloalkane amino acid .beta.-turn mimetics," Peptides 1994 Proceedings of the 23.sup.rd European Peptide Symposium, H.L.S. Maia (ed.), 1995, pp. 696-697.
Lombart and Lubell, "Synthesis of Enantiopure .alpha.,.omega.-Diamino dicarboxylates and Azabicycloalkane Amino Acids by Claisen Condensation of .alpha.-[N-(Phenylflourenyl)amino] Dicarboxylates," The Journal of Organic Chemistry 59(21): 6147-6149, 1994.
Marchand-Brynaert et al., "New .gamma.-Lactam Homologs Of Penems," Bioorganic & Medicinal Chemistry Letters 3(11): 2303-2308, 1993.
Mueller and Revesz, "Synthesis of 6,5-Fused Bicyclic Lactams as Potential Dipeptide .beta.-Turn Mimetics," Tetrahedron Letters 35(24): 4091-4092, 1994.
Nagai and Kato, "Synthesis of Phenyl-substituted BTD (bicyclic-turned dipeptide) and its incorporation into bioactive peptides," Peptides Proceedings of the 11.sup.th American Peptide Symposium, J.E. Rivier and G.R. Mars

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

.beta.-sheet mimetics and use thereof as protease inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with .beta.-sheet mimetics and use thereof as protease inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and .beta.-sheet mimetics and use thereof as protease inhibitors will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-937680

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.