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WO2002003993A3 - Use of inhibitors to multidrug resistance protein 5 (mrp5) to enhance intracellular levels of cyclic nucleotides - Google Patents

Use of inhibitors to multidrug resistance protein 5 (mrp5) to enhance intracellular levels of cyclic nucleotides Download PDF

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Publication number
WO2002003993A3
WO2002003993A3 PCT/EP2001/008077 EP0108077W WO0203993A3 WO 2002003993 A3 WO2002003993 A3 WO 2002003993A3 EP 0108077 W EP0108077 W EP 0108077W WO 0203993 A3 WO0203993 A3 WO 0203993A3
Authority
WO
WIPO (PCT)
Prior art keywords
mrp5
intracellular levels
inhibitors
cyclic nucleotides
inhibitor
Prior art date
Application number
PCT/EP2001/008077
Other languages
French (fr)
Other versions
WO2002003993A2 (en
Inventor
Gabriele Jedlitschky
Dietrich Keppler
Original Assignee
Deutsches Krebsforsch
Gabriele Jedlitschky
Dietrich Keppler
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE2000133880 external-priority patent/DE10033880A1/en
Application filed by Deutsches Krebsforsch, Gabriele Jedlitschky, Dietrich Keppler filed Critical Deutsches Krebsforsch
Priority to AU2001276403A priority Critical patent/AU2001276403A1/en
Publication of WO2002003993A2 publication Critical patent/WO2002003993A2/en
Publication of WO2002003993A3 publication Critical patent/WO2002003993A3/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
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Molecular Biology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a novel method for enhancing intracellular levels of cyclic nucleotides, in particular cyclic guanosine monophosphate (cGMP). The method involves administering to a host a therapeutically effective amount of an inhibitor to both MRP5 and phosphodiesterase or administering an inhibitor to MRP5 in combination with an inhibitor to phosphodiesterases. Also, methods for the identification of MRP5 inhibitors, for treating conditions under which higher intracellular levels of cGMP are desirable or for treating MRP5-mediated drug resistance are provided.
PCT/EP2001/008077 2000-07-12 2001-07-12 Use of inhibitors to multidrug resistance protein 5 (mrp5) to enhance intracellular levels of cyclic nucleotides WO2002003993A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001276403A AU2001276403A1 (en) 2000-07-12 2001-07-12 Use of inhibitors to multidrug resistance protein 5 (mrp5) to enhance intracellular levels of cyclic nucleotides

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE2000133880 DE10033880A1 (en) 2000-07-12 2000-07-12 Enhancing intracellular levels of a cyclic nucleotide, useful to treat e.g. chemotherapy resistance, comprises administering inhibitors of multidrug resistance protein 5 and phosphodiesterase
DE10033880.1 2000-07-12
US24697700P 2000-11-13 2000-11-13
US60/246,977 2000-11-13

Publications (2)

Publication Number Publication Date
WO2002003993A2 WO2002003993A2 (en) 2002-01-17
WO2002003993A3 true WO2002003993A3 (en) 2002-08-08

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/008077 WO2002003993A2 (en) 2000-07-12 2001-07-12 Use of inhibitors to multidrug resistance protein 5 (mrp5) to enhance intracellular levels of cyclic nucleotides

Country Status (2)

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AU (1) AU2001276403A1 (en)
WO (1) WO2002003993A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10352511A1 (en) * 2003-11-07 2005-06-16 Ernst-Moritz-Arndt-Universität Greifswald Use of MRP4 inhibitors for the treatment and / or prophylaxis of cardiovascular diseases
CN118324864B (en) * 2024-04-30 2025-02-14 南方科技大学 Peptide inhibitors targeting human multidrug resistance-associated protein MRP5

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994028902A1 (en) * 1993-06-09 1994-12-22 Pfizer Limited Pyrazolopyrimidinones for the treatment of impotence
WO2000033848A1 (en) * 1998-12-08 2000-06-15 The Rockefeller University Methods and compositions for prevention and treatment of restenosis with non-steroidal anti-inflammatory drugs
DE10004289A1 (en) * 2000-02-01 2001-08-02 Stief Christian Treatment of erectile dysfunction without causing undesirable side-effects, using phosphodiesterase IV inhibitor, optionally in combination with other phosphodiesterase inhibitor or adenylate cyclase stimulant

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994028902A1 (en) * 1993-06-09 1994-12-22 Pfizer Limited Pyrazolopyrimidinones for the treatment of impotence
WO2000033848A1 (en) * 1998-12-08 2000-06-15 The Rockefeller University Methods and compositions for prevention and treatment of restenosis with non-steroidal anti-inflammatory drugs
DE10004289A1 (en) * 2000-02-01 2001-08-02 Stief Christian Treatment of erectile dysfunction without causing undesirable side-effects, using phosphodiesterase IV inhibitor, optionally in combination with other phosphodiesterase inhibitor or adenylate cyclase stimulant

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BANSI ET AL: "TREQUINSIN,A POTENT NEW ANTIHYPERTENSIVE VASODILATATOR IN THE SERIES OF 2-(ARYLIMINO)-3-ALKYL-9,10-DIMETHOXY-3,4,6,7-TETRAHYDRO-2H-PYRIMID O(6,1-A)ISOQUINOLINE-4-ONES", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 11, no. 27, 1984, pages 1470 - 1480, XP002076161, ISSN: 0022-2623 *
DUFFY C P ET AL: "Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of non-steroidal anti-inflammatory drugs (NSAIDs).", EUROPEAN JOURNAL OF CANCER, vol. 34, no. 8, July 1998 (1998-07-01), pages 1250 - 1259, XP002198488, ISSN: 0959-8049 *
ICHINOSE F ET AL: "SELECTIVE PULMONARY VASODILATION INDUCED BY AEROSOLIZED ZAPRINAST", ANESTHESIOLOGY, AMERICAN SOCIETY OF ANESTHIOLOGISTS, PHILADELPHIA, PA,, US, vol. 88, no. 2, 1998, pages 410 - 416, XP000913484, ISSN: 0003-3022 *
JEDLITSCHKY: "The multidrug Resistance Protein 5 Functions as an ATP-dependent Export Pump for Cyclic Nucleotides", JBC PAPERS IN PRESS, 11 July 2000 (2000-07-11), DOI 10.1074/jbc.M005463200, pages 30069 - 30074, XP002198487 *

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Publication number Publication date
WO2002003993A2 (en) 2002-01-17
AU2001276403A1 (en) 2002-01-21

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