Phenylalanine enamide derivatives

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C546S122000

Reexamination Certificate

active

07122556

ABSTRACT:
Phenylalanine enamide derivatives of formula (1) are described:whereinR1is a group Ar1L2Ar2Alk— in which:Ar1is an optionally substituted aromatic or heteroaromatic group;L2is a covalent bond or a linker atom or group;Ar2is an optionally substituted arylene or heteroarylene group;and Alk is a chainin which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof;X is an —O— or —S— atom or —N(R2)— group in which:Rx, Ryand Rzwhich may be the same or different is each a hydrogen atom or an optional substituent;or Rzis an atom or group as previously defined and Rxand Ryare joined together to form an optionally substituted spiro linked cycloaliphatic or heterocycloaliphatic group;and the salts, solvates, hydrates and N-oxides thereof.The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immuno or inflammatory disorders or disorders involving the inappropriate growth or migration of cells.

REFERENCES:
patent: 3938367 (1976-02-01), Fletcher et al.
patent: 6835738 (2004-12-01), Brown et al.
patent: 6872719 (2005-03-01), Brown et al.
patent: WO 00/23419 (2000-04-01), None
patent: WO 00/32575 (2000-06-01), None
patent: WO 00/73260 (2000-12-01), None
patent: WO 01/79173 (2001-10-01), None
Boehncke et al. Experimental Dermatology (2005): 14: 70-80.
Abraham, W.M. et al., “α4-Integrins Mediate Antigen-Induced Late Bronchial Responses and Prolonged Airway Hyperresponsiveness in Sheep,”J. Clin. Invest., 1994, 93, 776-787.
Alhaique, F., et al., “Cyclisation of dinitriles by sodium alkoxides a new synthesis of naphthyridines,”Tetrahedron Letters, 1975, 3, 173-174.
Alhaique, F. et al., “91/Studies on 2,6-Naphthyridine: Hydrogenated Derivatives and a New Ring-Closure Reaction,”Gazzetta Chimica Italiana, 1975, 105, 1001-1009.
Ames, D.E., et al., “Condensation of β-dicarbonyl compounds with halogenepyridinecarb-oxylic acids. A convenient synthesis of some naphthyridine derivatives,”J.C.S. Perkin I, 1972, 705-710.
Aust, J. Chem., 433 (1972).
Baldwin, J. J. et al., “A Novel Naphthridinone Synthesis via Enamine Cyclization,”J. Org. Chem., 1978, 43(25), 4878-4880.
Berlin, C. et al., “α4β7 Integrin Mediates Lymphocyte Binding to the Mucosal Vascular Addressin MAdCAM-1,”Cell, 1993, 74, 185-195.
Binns, R.M. et al., “The Role of E-Selectin in Lymphocyte and Polymorphonuclear Cell Recruitment into Cutaneous Delayed Hypersensitivity Reactions in Sensitized Pigs,”J. Immunol., 1996, 157, 4094-409.
Birskin, M.J. et al., “Structural Requirements for Mucosal Vascular Addressin Binding to Its Lymphocyte Receptor α4β7,”J. Immunol., 1996, 156, 719-726.
Bodor, N., “Novel approaches in prodrug design,”Alfred Benzon Symposium, 1982, 17, 156-177.
Bordner, J. et al., “1,3-Diamino-6,7-dimethoxyisoquinoline Derivatives as Potential α1-Adrenoceptor Antagonist,”J. Med Chem., 1988, 31, 1036-1039.
Brooks, Peter C., et al., “Antiintegrin αvβ3 blocks human breast cancer growth and angiogenesis in human skin,”J. Clin. Invest., 1995, 96, 1815-1822.
Brun, E. M. et al., “Dienediolates of α,β-Unsaturated Carboxylic Acids in Synthesis: A New Synthetic Method to 2-Pyridones,”Synlett, 1999, 7, 1088-1090.
Brun, E. M. et al., “A New Synthetic Method to 2-Pyridones,”Synthesis, 2000, 2, 273-280.
Bundgaard, H.,Design of Prodrugs, 1985, Elsevier, Amsterdam.
Cardarelli, P.M. et al., “Cyclic RGD Peptide Inhibits α4β7 Interaction with Connecting Segment 1 and Vascular Cell Adhesion Molecule,”J. Biol. Chem., 1994, 269(28), 18668-18673.
Comprehensive Organic Functional Group Transformations, Ed. Katritzky et al, vol. 1-7, 1995 (Pergamon).
Comprehensive Heterocyclic Chemistry, Ed. Katritzky et al, vols. 1-8, 1984 and vols. 1-11, 1994 (Pergamon).
Comprehensive Organic Synthesis, Ed. Trost and Flemming, vols. 1-9, (Pergamon, 1991).
Deady, L. W. et al., “Ethoxycarbonylation of α-Cyano-o-toluonitrile and Cyclization to Isoquinolines and Pyrimido[4,5-c]isoquinolines,”Aust. J. Chem., 1989, 42, 1029-1034.
Encyclopedia of Reagents for Organic Synthesis, Ed. Paquette, vols. 1-8 (John Wiley and Sons, 1995).
Erle, D.J., et al., “Expression and function of the MadCAM-1 receptor, integrin α4β7, on human leukocytes,”J. Immunol., 1994, 153, 517-528.
Ezcurra, J. E. et al, “Synthesis of o-Quinodimethanes and Benzocyclobutenes from Dimethyl Squarte,”Tetrahedron Lett, 1993 34(39), 6177-80.
Falk, H. et al., On the Chemistry of Pyrrole Pigments, XCI [1]: Copper Complexes of Pyridinologous Linear Tri- and Tetra-pyrroles as Cyclopropanation Catalysts,Monatshefe Für Chemie, 1994, 125, 325-333.
Ferguson, T.A. et al., “Two integrin-binding peptides abrogate T cell-mediated immune responsesin vivo, ” Proc. Natl. Acad. Sci. USA, 1991, 88, 8072-8076.
Fieser and Fieser's Reagents for Organic Synthesis, vols. 1-19 (John Wiley and Sons, 1999).
Giacomello, et al., “Synthesis of 2,6-naphthyridine,”Tetra. Letters, 1965, 16, 1117-1121.
Green, T. W. in “Protective Groups in Organic Synthesis”, John Wiley and Sons, 1999.
Hammes, H., et al., “Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization,”Nature Medicine, 1996, 2, 529-533.
Heileman, M. J. et al., “New Metathesis Methodology Leading to Angularly-Fused Polycyclic Quinones and Related Compounds,”J. Am. Chem. Soc., 1998, 120, 3801-2.
Hergueta, R. A., et al., “Rearrangements of Cyclobutenones. Synthesis of N-Methyl-7,8-dihydrobenzophinanthridine-9,12-diols and Related Compounds,”J. Org. Chem., 1999, 64, 5979-83.
Hesterberg, P.E. et al, “Rapid Resolution of Chronic Colitis in the Cotton-top Tamarin With an Antibody to a Gut-Homing Integrin α4β7,”Gastroenterol, 1996 111, 1373-80.
Hiebl, J., “New Synthesis of isoquinoline-3-carboxylates,”Tetrahedron Letters 40, 1999, 7935-7938.
Hodivala-Dilke, K.M., “β3-integrin-deficient mice are a model for glanzmann thrombasthenia showing placental defects and reduced survival,”J. Clin. Invest., 1999, 103(2), 229-238.
Holzmann, B., et al., “Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like α chain associated with either of two integrin β chains, one of which is novel,”EMBO J., 1989, 8(6), 1735-1741.
Humphries, M.J. et al., “Mechanisms of VCAM-1 and fibronectin binding to integrin α4β1: implications for integrin function and rational drug design,”Ciba Foundation Symposium, 1995, 189, 177-194.
Issekutz, T.B., “Inhibition of Lymphocyte Endothelial Adhesion and In Vivo Lymphocyte Migration to Cutaneous Inflammation by TA-3, a New Monoclonal Antibody to Rat LFA-1,”J. Immunol., 1992, 149(10), 3394-3402.
Kaiser, E. M. et al., “Facile Synthesis of 1-Amino-3-arylisoquinolines,”Synthesis, Nov. 1974, 11, 805-6.
Kocienski, P. et al., “A Synthesis of (-)-Tetrahydrosipstatin,”Tetrahedron Lett., Jan. 17, 1989, 30, 1833-1836.
Kraus, J. L. et al., “Sur La Reactivite Du Squarate De Dimethyle Vis-á-vis De Thiols,”Tetrahedron Lett., 1987, 28, 1765-8.
Larock's Comprehensive Organic Transformations(VCH Publishers Inc., 1989).
Li, Z. et al., “Effect of an anti-Mol MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs,”Am. J. Physiol., 1992, 263(6 Pt 1), L723-726.
MacDougall, J. M. et al, J. Org. Chem, 64 5979-83 (1999).
March's Advanced Organic Chemistry(John Wiley and Sons, 1992).
Marlin, S.D. et al., “LFA-1 Immunodeficiency Disease,”J. Exp. Med., 1986, 164, 855-867.
Mitjans, F., et al., “An anti-αv-integrin antibody that blocks integrin

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

Phenylalanine enamide derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Phenylalanine enamide derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Phenylalanine enamide derivatives will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3676477

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