Lysophosphatidic acid receptor selective antagonists

Details Lysophosphatidic acid receptor selective antagonists Lysophosphatidic acid receptor selective antagonists

2005-05-06

2010-10-26

Shiao, Rei-tsang (Department: 1628)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C546S022000

Reexamination Certificate

active

07820703

ABSTRACT:
The present invention is directed to compositions comprising lysophosphatidic acid analogs and methods of using such analogs as agonist or antagonists of LPA receptor activity. In addition the invention is directed to LPA receptor agonists that vary in the degree of selectivity at individual LPA receptors (i.e. LPA1, LPA2 and LPA3). More particularly the present invention is directed to LPA analogs wherein the glycerol is replaced with ethanolamine and a variety of substitutions have been linked at the second carbon atom.

REFERENCES:
patent: RE29829 (1978-11-01), Bordenca et al.
patent: 4331685 (1982-05-01), Tokuda et al.
patent: 4845292 (1989-07-01), McGregor et al.
patent: 4906767 (1990-03-01), Mathias et al.
patent: 5219884 (1993-06-01), Fujita et al.
patent: 5307308 (1994-04-01), Noguchi
patent: 5405988 (1995-04-01), Klar et al.
patent: 5604229 (1997-02-01), Fujita et al.
patent: 5773475 (1998-06-01), Kohn et al.
patent: 6380177 (2002-04-01), Erickson
patent: 7169818 (2007-01-01), Lynch et al.
patent: 4225488 (1992-07-01), None
patent: 1 156 054 (2004-04-01), None
patent: WO 96/18600 (1996-06-01), None
patent: WO 96/31124 (1996-10-01), None
patent: WO 98/45249 (1998-10-01), None
patent: WO/99 047101 (1999-09-01), None
patent: WO 01/57057 (2001-08-01), None
patent: WO 01/71022 (2001-09-01), None
patent: WO 02/06268 (2002-01-01), None
patent: WO/02 29001 (2002-04-01), None
patent: WO 02/018395 (2002-07-01), None
Heasley et al., Bioorganic & Medicinal Chemistry, 2004, 14(11), pp. 2735-2740.
Bektas, Meryem et al. The G Protein-Coupled Receptor GPR4 Suppresses ERK Activation in a Ligand-Independent Manner. Biochemistry. 2003. vol. 42, 12181-12191.
Choi, D. et al. Synthesis and Anticonvulsant Activities of N-Benzyl-2-acetamidopropionamide Derivatives, J. Med. Chem., 1996.vol. 39, 1907-1916.
Ferry, Gilles et al. A Nanomolar Inhibitor of Autotaxin : Discovery, Synthesis and Applications as a Pharmacological Tool. J. Pharmacology And Experimental Therapeutics. 2008. vol. 327, No. 3, 809-819.
Gajewiak, Joanna et al. Alkoxymethylenephosphonate Analogues of (Lyso) phosphatidic Acid Stimulate Signaling Networks Coupled to the LPA2Receptor. Chem. Med. Chem. 2007. vol. 2, 1789-1798.
Heasley, Brian H. et al. Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3receptor antagonist. Bioorganic & Medicinal Chemistry Letters. 2004. 2735-2740.
Heasley, Brian H. et al. A novel series of 2-pyridyl-containing compounds as lysophosphatidic acid receptor antagonists: development of a nonhydrolyzable LPA3receptor-selective antagonist. Bioorganic & Medicinal Chemistry Letters. 2004. 4069-4074.
Jiang, Guowei et al. α-Substituted Phosphonate Analogues of Lysophosphatidic Acid (LPA) Selectively Inhibit Production and Action of LPA. Chem. Med. Chem. 2007. vol. 2, 679-690.
Santos, Webster L., et al. The Molecular Pharmacology of Lysophosphatidate Signaling. Annals New York Academy of Sciences. 2000. vol. 905, 232-241.
Santos, Webster L. et al. Synthesis and biological evaluation of phosphonic and thiophosphoric acid derivatives of lysophosphatidic acid. Bioorganic & Medicinal Chemistry Letters. 2004. 3473-3476.
Sturtz, Georges et al. About an original pharmacomodulation approach of methotrexate: synthesis of gem-diphosphonic amethopterine and N-10 deaza analogs. Academie des Sciences. 1990. 739-742.
Sturtz, Georges et al. Analogues phosphonoglutamiques d'amethopterine (methotrexate). Eur. J. Med. Chem. 1984. vol. 19, No. 3, 267-273.
Sturtz,G., et al. A study of the deliver-targeting concept applied to antineoplastic drugs active on human osteosarcoma. I. Synthesis & biolocial activity in nude mice carrying human osteosarcoma xenografts of gem-bisphosphonic methotrexate analogues.Eur. J. Med. Chem. 1992., vol. 27, 825-833.
Sugiura, Takayuki et al. Biochemical Characterization of the Interaction of Lipid Phosphoric Acids with Human Platelets: Comparison with Platelet Activating Factor. Archives of Biochemistry & Biophysics. 1994. vol. 311(2), 358-368.
Tsukamoto, Takashi et al. Mechanism-Based Inhibition of Human Folypolyglutamate Synthetase: Design, Synthesis, and Biochemical Characterization of a Phophapeptide Mimic of the Tetrahedral Intermediate. Archives of Biochemistry & Biophysics, 1998. vol. 355(1),109-118.
Xu, Yong et al. Alkyl lysophosphatidic acid and fluoromethylene phosphonate analogs as metabolically-stabilized agonists for LPA receptors. Bioorganic & Medicinal Chemistry Letters. 2004. 5323-5328.
Xu, Yong et al. Structure-Activity Relationships of Fluorinated Lysophosphatidic Acid Analogues. J. Medicinal Chemistry. 2005. vol. 48, 3319-3327.
Hopper et al., “Facile synthesis of lysophospholipids Containing unsaturated fatty acid chains,” Tetrahedron Letters, vol. 37 ( No. 44), p. 7871-7874, 1996.
Heise, C. et al., Molecular Pharmacology, 60, 1173-1180, (2001).
Ortiz, A., et al., J. Med. Chem., 38, 2681-2691, (1995): Erratum 40, 4168, (1997).
Lynch, K., et al., Molecular Pharmacology, 52, 75-81, (1997).

Affiliated with

Also associated with

Rating

Lysophosphatidic acid receptor selective antagonists does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Lysophosphatidic acid receptor selective antagonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lysophosphatidic acid receptor selective antagonists will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4161114