WO2003028712A3 - Purinergic and pyrimidinergic receptor agonists for the treatment of activated cd4+ t lymphocyte-mediated immune diseases - Google Patents

Purinergic and pyrimidinergic receptor agonists for the treatment of activated cd4+ t lymphocyte-mediated immune diseases Download PDF

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Publication number
WO2003028712A3
WO2003028712A3 PCT/EP2002/010954 EP0210954W WO03028712A3 WO 2003028712 A3 WO2003028712 A3 WO 2003028712A3 EP 0210954 W EP0210954 W EP 0210954W WO 03028712 A3 WO03028712 A3 WO 03028712A3
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WIPO (PCT)
Prior art keywords
purinergic
represent
independently
receptor agonists
lymphocyte
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Application number
PCT/EP2002/010954
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French (fr)
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WO2003028712A2 (en
Inventor
Liliane Schandene
Michel Goldman
Xavier Duhant
Jean-Marie Boeynaems
Didier Communi
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Univ Bruxelles
Liliane Schandene
Michel Goldman
Xavier Duhant
Jean-Marie Boeynaems
Didier Communi
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Application filed by Univ Bruxelles, Liliane Schandene, Michel Goldman, Xavier Duhant, Jean-Marie Boeynaems, Didier Communi filed Critical Univ Bruxelles
Publication of WO2003028712A2 publication Critical patent/WO2003028712A2/en
Publication of WO2003028712A3 publication Critical patent/WO2003028712A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention in particular relates to the use of purinergic and pyrimidinergic receptor agonists of formula (1) or a pharmaceutically acceptable salt thereof for inhibition of CD4+ T lymphocytes activation or as an immunosuppressive agent, wherein B1 is adenine or uracil, optionally substituted by thioalkyl, R1 and R2 represent each independently OH, H, OR7, OCOR7, OCOR7COR7, wherein R7 represents alkyl or aryl and X is of formula (2), (3) or (4), wherein R10 represents hydrogen or is of formula (7),wherein B2 is selected from the group comprising adenine, uracil, thymine, cytosine, guanine, xanthine and hypoxanthine, optionally substituted by thioalkyl, wherein n is 0, 1, 2, 3 or 4, and wherein R4, R4a and R4b represent each independently O, NH, alkylene, monohaloalkylene or dihaloalkylene and R3, R5, R6, R8, R9 represent each independently OH or SH, and wherein R11 and R12 represent each independently OH, H, OR7, OCOR7, OCOR7COR7, wherein R7 is as defined above.
PCT/EP2002/010954 2001-09-28 2002-09-30 Purinergic and pyrimidinergic receptor agonists for the treatment of activated cd4+ t lymphocyte-mediated immune diseases WO2003028712A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP01870207 2001-09-28
EP01870207.6 2001-09-28
US33846401P 2001-12-05 2001-12-05
US60/338,464 2001-12-05

Publications (2)

Publication Number Publication Date
WO2003028712A2 WO2003028712A2 (en) 2003-04-10
WO2003028712A3 true WO2003028712A3 (en) 2003-12-18

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Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006038865A1 (en) * 2004-10-01 2006-04-13 Betagenon Ab Nucleotide derivatives for the treatment of type 2 diabetes and other disorders
US7820637B2 (en) 2005-03-17 2010-10-26 Proyecto De Biomedicina Cima, S.L. Use of 5′-methylthioadenosine (MTA) in the prevention and/or treatment of autoimmune diseases and/or transplant rejection
WO2007020018A1 (en) * 2005-08-12 2007-02-22 Universite Libre De Bruxelles Use of purinergic and pyrimidinergic receptor agonists for dendritic cells based immunotherapies
EP3962493A2 (en) 2019-05-03 2022-03-09 Flagship Pioneering Innovations V, Inc. Methods of modulating immune activity/level of irf or sting or of treating cancer, comprising the administration of a sting modulator and/or purinergic receptor modulator or postcellular signaling factor

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040166A1 (en) * 1995-06-07 1996-12-19 Hostetler Karl Y Nucleotide analogues for topical treatment of proliferative disease of the skin
US5900407A (en) * 1997-02-06 1999-05-04 Inspire Pharmaceuticals, Inc. Method of treating dry eye disease with uridine triphosphates and related compounds
WO1999043326A1 (en) * 1998-02-24 1999-09-02 The Trustees Of The University Of Pennsylvania Use of a cardiac purinoceptor to effect cellular glucose uptake
DE19812930A1 (en) * 1998-03-24 1999-09-30 Europ Lab Molekularbiolog Determination of effect of reactive oxygen intermediates on target molecule using cell-free system
WO2000001349A2 (en) * 1998-07-01 2000-01-13 The Trustees Of The University Of Pennsylvania Cavity induced allosteric modification of intermolecular interactions and methods of identifying compounds that effect the same
WO2000025758A1 (en) * 1998-11-04 2000-05-11 Supergen, Inc. Oral administration of adenosine analogs
US6143279A (en) * 1997-08-29 2000-11-07 The University Of North Carolina At Chapel Hill Uridine 5'-diphosphate and analogs useful for treating lung diseases
WO2001007054A1 (en) * 1999-07-22 2001-02-01 Supergen, Inc. Methods for treating autoimmune diseases
WO2001082934A1 (en) * 2000-04-28 2001-11-08 University Of Pittsburgh Intraperitoneal administration of adenosine for the treatment or prevention of gastrointestinal or systemic diseases
US20010046497A1 (en) * 2000-04-21 2001-11-29 Zhang Fang Liang G-protein coupled receptor and methods
WO2003000056A1 (en) * 2001-06-25 2003-01-03 Inspire Pharmaceuticals, Inc. Joint lubrication with p2y purinergic receptor agonists
WO2003039473A2 (en) * 2001-11-06 2003-05-15 Inspire Pharmaceuticals, Inc. Method for treating or preventing inflammatory diseases

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040166A1 (en) * 1995-06-07 1996-12-19 Hostetler Karl Y Nucleotide analogues for topical treatment of proliferative disease of the skin
US5900407A (en) * 1997-02-06 1999-05-04 Inspire Pharmaceuticals, Inc. Method of treating dry eye disease with uridine triphosphates and related compounds
US6143279A (en) * 1997-08-29 2000-11-07 The University Of North Carolina At Chapel Hill Uridine 5'-diphosphate and analogs useful for treating lung diseases
WO1999043326A1 (en) * 1998-02-24 1999-09-02 The Trustees Of The University Of Pennsylvania Use of a cardiac purinoceptor to effect cellular glucose uptake
DE19812930A1 (en) * 1998-03-24 1999-09-30 Europ Lab Molekularbiolog Determination of effect of reactive oxygen intermediates on target molecule using cell-free system
WO2000001349A2 (en) * 1998-07-01 2000-01-13 The Trustees Of The University Of Pennsylvania Cavity induced allosteric modification of intermolecular interactions and methods of identifying compounds that effect the same
WO2000025758A1 (en) * 1998-11-04 2000-05-11 Supergen, Inc. Oral administration of adenosine analogs
WO2001007054A1 (en) * 1999-07-22 2001-02-01 Supergen, Inc. Methods for treating autoimmune diseases
US20010046497A1 (en) * 2000-04-21 2001-11-29 Zhang Fang Liang G-protein coupled receptor and methods
WO2001082934A1 (en) * 2000-04-28 2001-11-08 University Of Pittsburgh Intraperitoneal administration of adenosine for the treatment or prevention of gastrointestinal or systemic diseases
WO2003000056A1 (en) * 2001-06-25 2003-01-03 Inspire Pharmaceuticals, Inc. Joint lubrication with p2y purinergic receptor agonists
WO2003039473A2 (en) * 2001-11-06 2003-05-15 Inspire Pharmaceuticals, Inc. Method for treating or preventing inflammatory diseases

Non-Patent Citations (1)

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Title
HILLAIRE-BUYS D ET AL: "Purinergic receptors on insulin-secreting cells.", FUNDAMENTAL & CLINICAL PHARMACOLOGY, vol. 8, no. 2, 1994, pages 117 - 127, XP009012619, ISSN: 0767-3981 *

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