WO1994007507A1 - Procede d'inhibition de l'activite de l'inositol 1,4,5-triphosphate - Google Patents
Procede d'inhibition de l'activite de l'inositol 1,4,5-triphosphate Download PDFInfo
- Publication number
- WO1994007507A1 WO1994007507A1 PCT/US1993/008168 US9308168W WO9407507A1 WO 1994007507 A1 WO1994007507 A1 WO 1994007507A1 US 9308168 W US9308168 W US 9308168W WO 9407507 A1 WO9407507 A1 WO 9407507A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- inositol
- triphosphate
- binding
- calcium
- release
- Prior art date
Links
Classifications
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/795—Polymers containing sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This application relates to a series of diamino benzenedisulfonic acid oligomers that have demonstrated an affinity for the receptor sites of inositol 1,4,5- triphosphate (IP 3 ) and are, therefore useful in diminishing the bioactivity of IP 3 , especially with regard to its effect on the release of intracellular calcium ions.
- IP 3 inositol 1,4,5- triphosphate
- IP 3 inositol 1,4,5-triphosphate
- Inositol 1,4,5-triphosphate IP 3
- IP 3 acts to stimulate the release of calcium ions from storage organelles within
- IP 3 is characterized as a "second messenger".
- the calcium released by IP 3 functions to stimulate a variety of physiologic processes such as smooth muscle contraction, histamine secretion and the hyperpolarization of nerve
- Any compound or agent that can promote or interfere with the function of IP 3 will promote or interfere with the generation of calcium ions and thereby elicit predictable pharmacological effects.
- IP 3 releases calcium ions begins with the binding of IP 3 to a specific receptor protein located on an intracellular calcium storage compartment located typically on the endoplasmic reticulum. This receptor protein has been cloned and has been shown to form
- IP 3 binds with its receptor, a calcium channel is opened causing the release of calcium stored in the cell's endoplasmic reticulum. In turn, the released calcium will elicit the appropriate cellular response.
- the diamino benzenedisulfonic acid oligomers of this invention also appear to antagonize the effects of IP 3 by competing for the receptor site. In most cases, these compounds are more effective than heparin and demonstrate fewer secondary effects.
- these compounds are more effective than heparin and demonstrate fewer secondary effects.
- the oligomers of this invention would also be administered to modulate IP 3 -induced calcium release and have a salutary effect on any number of disorders that are caused or exacerbated by an inordinately productive IP 3 second messenger pathway.
- Specific binding was defined as the difference between total binding (radioactivity in the absence of test compound and cold IP 3 ) and non-specific binding
- the y-axis represents the concentration of free calcium ions in arbitrary units.
- the tracing shows that two successive additions of 0.1 ⁇ M of IP 3 stimulated similar amounts of calcium ion release from cerebellar microsomes.
- the addition of 1 ⁇ M of MDL 102,869 stimulated a small increase of calcium ion for unknown reasons.
- calcium ion release stimulated by 0.1 ⁇ M of IP 3 was inhibited by 42%. This inhibition was overcome by the addition of 1 ⁇ M of IP 3 , consistent with competitive antagonism by MDL 102,869.
- n is a whole number within the range of 5-20 and the pharmaceutically acceptable salts thereof.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Polyurethanes Or Polyureas (AREA)
Abstract
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019950701166A KR950703347A (ko) | 1992-09-28 | 1993-08-30 | 이노시톨 1,4,5-트리포스페이트의 길항 방법(Method for Antagonizing Inositol 1,4,5-Triphosphate) |
AU48417/93A AU670962B2 (en) | 1992-09-28 | 1993-08-30 | Method for antagonizing inositol 1,4,5-triphosphate |
EP93921252A EP0661982A1 (fr) | 1992-09-28 | 1993-08-30 | Procede d'inhibition de l'activite de l'inositol 1,4,5-triphosphate |
JP6509054A JPH08502068A (ja) | 1992-09-28 | 1993-08-30 | イノシトール1,4,5‐トリスホスフェートを拮抗する方法 |
NO951163A NO951163L (no) | 1992-09-28 | 1995-03-27 | Metode for antagonisering av inositol-1,4,5-trifosfat |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US95239392A | 1992-09-28 | 1992-09-28 | |
US07/952,393 | 1992-09-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994007507A1 true WO1994007507A1 (fr) | 1994-04-14 |
Family
ID=25492868
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1993/008168 WO1994007507A1 (fr) | 1992-09-28 | 1993-08-30 | Procede d'inhibition de l'activite de l'inositol 1,4,5-triphosphate |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0661982A1 (fr) |
JP (1) | JPH08502068A (fr) |
KR (1) | KR950703347A (fr) |
AU (1) | AU670962B2 (fr) |
CA (1) | CA2145681A1 (fr) |
HU (1) | HUT70192A (fr) |
IL (1) | IL107066A (fr) |
MX (1) | MX9305933A (fr) |
NO (1) | NO951163L (fr) |
NZ (1) | NZ256178A (fr) |
TW (1) | TW260663B (fr) |
WO (1) | WO1994007507A1 (fr) |
ZA (1) | ZA936978B (fr) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996000586A3 (fr) * | 1994-06-30 | 1996-02-15 | Max Planck Gesellschaft | Methodes de traitement d'affections a proliferation cellulaire par modulation de la transduction du signal |
WO1997022251A1 (fr) * | 1995-12-21 | 1997-06-26 | Ayurcore, Inc. | Compositions pour moduler la concentration de triphosphate d'inositol intracellulaire et utilisations de ces dernieres |
US5780483A (en) * | 1995-02-17 | 1998-07-14 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US5886044A (en) * | 1995-02-17 | 1999-03-23 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6005008A (en) * | 1996-02-16 | 1999-12-21 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6133319A (en) * | 1996-06-27 | 2000-10-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6211373B1 (en) | 1996-03-20 | 2001-04-03 | Smithkline Beecham Corporation | Phenyl urea antagonists of the IL-8 receptor |
US6262113B1 (en) | 1996-03-20 | 2001-07-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6271261B1 (en) | 1996-06-27 | 2001-08-07 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
WO2002038140A3 (fr) * | 2000-11-09 | 2003-03-13 | Contrimmune Biotechnology Inc | Utilisations therapeutiques de modulateurs du canal calcique induits par le recepteur ip¿3? |
US9771430B2 (en) | 2011-09-02 | 2017-09-26 | The Trustees Of Columbia University In The City Of New York | Method of treating a metabolic disorder induced by obesity in a subject in need thereof by administering MK2/3 inhibitors |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB781479A (en) * | 1953-08-27 | 1957-08-21 | Ciba Ltd | New polyureas and process for making them |
EP0467185A2 (fr) * | 1990-07-09 | 1992-01-22 | The Dow Chemical Company | Oligomères, leurs applications et formulations |
-
1993
- 1993-08-30 HU HU9500891A patent/HUT70192A/hu unknown
- 1993-08-30 WO PCT/US1993/008168 patent/WO1994007507A1/fr not_active Application Discontinuation
- 1993-08-30 AU AU48417/93A patent/AU670962B2/en not_active Ceased
- 1993-08-30 KR KR1019950701166A patent/KR950703347A/ko not_active Ceased
- 1993-08-30 NZ NZ256178A patent/NZ256178A/en unknown
- 1993-08-30 JP JP6509054A patent/JPH08502068A/ja active Pending
- 1993-08-30 CA CA002145681A patent/CA2145681A1/fr not_active Abandoned
- 1993-08-30 EP EP93921252A patent/EP0661982A1/fr not_active Ceased
- 1993-09-21 ZA ZA936978A patent/ZA936978B/xx unknown
- 1993-09-22 TW TW082107787A patent/TW260663B/zh active
- 1993-09-22 IL IL107066A patent/IL107066A/en not_active IP Right Cessation
- 1993-09-27 MX MX9305933A patent/MX9305933A/es unknown
-
1995
- 1995-03-27 NO NO951163A patent/NO951163L/no unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB781479A (en) * | 1953-08-27 | 1957-08-21 | Ciba Ltd | New polyureas and process for making them |
EP0467185A2 (fr) * | 1990-07-09 | 1992-01-22 | The Dow Chemical Company | Oligomères, leurs applications et formulations |
Non-Patent Citations (4)
Title |
---|
F. O'ROURKE ET AL.: "THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR BINDING SITES OF PLATELET MEMBRANES", THE BIOCHEMICAL JOURNAL, vol. 267, no. 2, 1990, pages 297 - 302 * |
M.A. TONES ET AL.: "THE EFFECT OF HEPARIN ON THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IN RAT LIVER MICROSOMES", FEBS LETTERS, vol. 252, no. 1,2, 1989, pages 105 - 108, XP025605443, DOI: doi:10.1016/0014-5793(89)80898-1 * |
See also references of EP0661982A1 * |
T.K. GHOSH ET AL.: "COMPETITIVE, REVERSIBLE, AND POTENT ANTAGONISM OF INOSITOL 1,4,5-TRISPHOSPHATE-ACTIVATED CALCIUM RELEASE BY HEPARIN", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 263, no. 23, 1988, pages 11075 - 11079 * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996000586A3 (fr) * | 1994-06-30 | 1996-02-15 | Max Planck Gesellschaft | Methodes de traitement d'affections a proliferation cellulaire par modulation de la transduction du signal |
US6180675B1 (en) | 1995-02-17 | 2001-01-30 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US5780483A (en) * | 1995-02-17 | 1998-07-14 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US5886044A (en) * | 1995-02-17 | 1999-03-23 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
WO1997022251A1 (fr) * | 1995-12-21 | 1997-06-26 | Ayurcore, Inc. | Compositions pour moduler la concentration de triphosphate d'inositol intracellulaire et utilisations de ces dernieres |
US6083920A (en) * | 1995-12-21 | 2000-07-04 | Ayurcore, Inc. | Compositions for modulating intracellular inositol trisphosphate concentration |
US6005008A (en) * | 1996-02-16 | 1999-12-21 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6262113B1 (en) | 1996-03-20 | 2001-07-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6211373B1 (en) | 1996-03-20 | 2001-04-03 | Smithkline Beecham Corporation | Phenyl urea antagonists of the IL-8 receptor |
US6133319A (en) * | 1996-06-27 | 2000-10-17 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
US6271261B1 (en) | 1996-06-27 | 2001-08-07 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
WO2002038140A3 (fr) * | 2000-11-09 | 2003-03-13 | Contrimmune Biotechnology Inc | Utilisations therapeutiques de modulateurs du canal calcique induits par le recepteur ip¿3? |
US9771430B2 (en) | 2011-09-02 | 2017-09-26 | The Trustees Of Columbia University In The City Of New York | Method of treating a metabolic disorder induced by obesity in a subject in need thereof by administering MK2/3 inhibitors |
Also Published As
Publication number | Publication date |
---|---|
AU670962B2 (en) | 1996-08-08 |
IL107066A0 (en) | 1993-12-28 |
NO951163D0 (no) | 1995-03-27 |
HU9500891D0 (en) | 1995-05-29 |
AU4841793A (en) | 1994-04-26 |
MX9305933A (es) | 1994-04-29 |
JPH08502068A (ja) | 1996-03-05 |
NZ256178A (en) | 1997-03-24 |
TW260663B (fr) | 1995-10-21 |
HUT70192A (en) | 1995-09-28 |
ZA936978B (en) | 1994-04-18 |
NO951163L (no) | 1995-03-27 |
IL107066A (en) | 1998-01-04 |
KR950703347A (ko) | 1995-09-20 |
EP0661982A1 (fr) | 1995-07-12 |
CA2145681A1 (fr) | 1994-04-14 |
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