WO2007009589A2 - Verwendung von aktivatoren der löslichen guanylatzyklase zur behandlung von raynaud phänomenen - Google Patents
Verwendung von aktivatoren der löslichen guanylatzyklase zur behandlung von raynaud phänomenen Download PDFInfo
- Publication number
- WO2007009589A2 WO2007009589A2 PCT/EP2006/006501 EP2006006501W WO2007009589A2 WO 2007009589 A2 WO2007009589 A2 WO 2007009589A2 EP 2006006501 W EP2006006501 W EP 2006006501W WO 2007009589 A2 WO2007009589 A2 WO 2007009589A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- treatment
- raynaud
- phenomenon
- medicament
- guanylate cyclase
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic 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
- A61K31/33—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
Definitions
- the present invention relates to the use of compounds of formulas I-VI for the manufacture of a medicament for the treatment of primary and secondary Raynaud's phenomenon.
- a distinction is a primary, uncomplicated Raynaud's phenomenon using an excessive physiological ⁇ reaction arteries of extremities to cold stimuli from a secondary Raynaud's phenomenon with systemic underlying disease from the rheumatic F ⁇ rmen Vietnamese or from the connective tissue disorders such as scleroderma, Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, polymyositis or dermatomyositis.
- the secondary Raynaud phenomenon is also often associated with tissue necrosis of the fingers, ulcerations and gangrene.
- vasodilators eg calcium channel blockers, cti-receptor blockers, nitro preparations and prostaglandin Often only cases and anecdotal reports on the different substances exist, with sometimes contradictory results.
- the individual vasodilating principles show response rates of ' only about 50%.' Side effects are common Intravenous prostaglandins are not yet approved for the indication Raynaud and studies with various prostaglandin derivatives (iloprost, beraprost, cicaprost) have not been shown to confer clinical benefit on the calcium channel blockers and ⁇ i receptor blockers systemic hypotension show his illness.
- cyclic guanosine monophosphate cGMP
- NO nitric oxide
- the guanylate cyclases catalyze the biosynthesis of cGMP from guanosine triphosphate
- the particular features of the ligand and the nature of the ligands are divided into two groups: the particulate natriuretic peptides stimulable guanylate cyclases and the soluble NO-stimulable guanylate cyclases.
- the soluble guanylate cyclases consist of two subunits and contain
- NO can bind to the iron atom of the heme and thus significantly increase the activity of the enzyme.
- heme-free preparations can not be stimulated by NO.
- CO is also capable of attacking the iron central atom of the heme, with stimulation by CO being significantly less than by NO.
- the NO / cGMP system may be suppressed, for example, hypertension, platelet activation, increased cell proliferation, endothelial dysfunction, atherosclerosis, angina pectoris, heart failure, thrombosis, stroke , sexual dysfunction and mayocardial infarction.
- a NO-independent treatment option for such diseases aimed at influencing the cGMP signaling pathway in organisms is a promising approach on account of the expected high efficiency and low side effects.
- stimulators of soluble guanylate cyclase are particularly suitable for the therapy of microangiopathies.
- the compounds according to the invention of formulas I to VI listed below have improved pharmacodynamic properties: they act vasodilating independently of the endogenously produced NO in the arterial end stream path even in the case of severe endothelial damage.
- the stimulators of soluble guanylate cyclase enhance the effect of the endogenously produced NO.
- Compound (I) corresponds to the following formula:
- Connection (FVa) corresponds to the following formula: (IVa).
- An additional embodiment of the present invention comprises the procedure for the prophylaxis and / or reduction of pulmonary hypertension using at least one of the compounds of formulas (I-VI).
- Another object of the present invention are pharmaceutical compositions containing at least one compound of the invention and at least one or more other active ingredients, in particular for the treatment and / or prophylaxis of the aforementioned diseases.
- the compounds according to the invention can act systemically and / or locally.
- they may be applied in a suitable manner, e.g. oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, dermal, transdermal, conjunctivae otic or as an implant or stent.
- the compounds according to the invention can be administered in suitable administration forms.
- Parenteral administration can be accomplished by bypassing a resorption step (e.g., intravenously, intraarterially, intracardially, intraspinal, or intralumbar) or by resorting to absorption (e.g., intramuscularly, subcutaneously, intracutaneously, percutaneously, or intraperitoneally).
- a resorption step e.g., intravenously, intraarterially, intracardially, intraspinal, or intralumbar
- absorption e.g., intramuscularly, subcutaneously, intracutaneously, percutaneously, or intraperitoneally.
- parenteral administration are suitable as application forms u.a. Injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates or sterile powders.
- pharmaceutical forms for inhalation include powder inhalers, nebulizers, nasal drops, solutions, sprays; tablets, wafers or capsules, suppositories paraben, vaginal capsules, aqueous suspensions (lotions, shake mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic systems (such as patches), milk, pastes, foams, powdered powders, implants or stents.
- the compounds according to the invention can be converted into the stated administration forms. This can be done in a conventional manner by mixing with inert, non-toxic, pharmaceutically suitable excipients.
- excipients for example microcrystalline cellulose, lactose, mannitol
- solvents for example liquid polyethylene glycols
- emulsifiers and dispersants or wetting agents for example sodium dodecyl sulfate, polyoxysorbitol oleate
- binders for example polyvinylpyrrolidone
- synthetic and natural polymers for example albumin
- Stabilizers for example, antioxidants such as ascorbic acid
- dyes eg, inorganic pigments such as iron oxides
- flavor and 7 odder odor correction for example microcrystalline cellulose, lactose, mannitol
- solvents for example liquid polyethylene glycols
- emulsifiers and dispersants or wetting agents for example sodium dodecyl sulfate, polyoxysorbito
- compositions containing at least one compound of the invention usually together with one or more inert, non-toxic, pharmaceutically suitable excipients, and their use for the purposes mentioned above.
- the formulations may contain, according to the procedure, active substance between 0.1 and 99% active ingredient, suitably 25-95% for tablets and capsules and 1-50% for liquid formulations, i. the active substance should be present in sufficient quantities to reach the stated dose latitude.
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008521831A JP2009501737A (ja) | 2005-07-16 | 2006-07-04 | レイノー現象の処置のための可溶性グアニル酸シクラーゼ活性化剤の使用 |
EP06762392A EP1917008A2 (de) | 2005-07-16 | 2006-07-04 | Verwendung von aktivatoren der löslichen guanylatzyklase zur behandlung von raynaud phänomenen |
US11/988,991 US20090215769A1 (en) | 2005-07-16 | 2006-07-04 | Use of soluble guanylate cyclase activators for the treatment of Raynaud's Phenomenon |
CA002615051A CA2615051A1 (en) | 2005-07-16 | 2006-07-04 | Use of soluble guanylate cyclase for the treatment of raynaud's phenomenon |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102005033370 | 2005-07-16 | ||
DE102005033370.2 | 2005-07-16 | ||
DE102005047945.6 | 2005-10-06 | ||
DE102005047945A DE102005047945A1 (de) | 2005-07-16 | 2005-10-06 | Verwendung von Aktivatoren der löslichen Guanylatzyklase zur Behandlung von Raynaud Phänomenen |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2007009589A2 true WO2007009589A2 (de) | 2007-01-25 |
WO2007009589A3 WO2007009589A3 (de) | 2007-08-16 |
Family
ID=37563587
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2006/006501 WO2007009589A2 (de) | 2005-07-16 | 2006-07-04 | Verwendung von aktivatoren der löslichen guanylatzyklase zur behandlung von raynaud phänomenen |
Country Status (6)
Country | Link |
---|---|
US (1) | US20090215769A1 (de) |
EP (1) | EP1917008A2 (de) |
JP (1) | JP2009501737A (de) |
CA (1) | CA2615051A1 (de) |
DE (1) | DE102005047945A1 (de) |
WO (1) | WO2007009589A2 (de) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9260424B2 (en) * | 2009-10-26 | 2016-02-16 | Auspex Pharmaceuticals, Inc. | 4,6-diaminopyrimidine stimulators of soluble guanylate cyclase |
CA2800709C (en) * | 2010-05-26 | 2017-04-04 | Claudia Hirth-Dietrich | The use of sgc stimulators, sgc activators, alone and combinations with pde5 inhibitors for the treatment of systemic sclerosis (ssc) |
DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
EP2594270A3 (de) * | 2011-11-18 | 2013-07-31 | BIP Patents | Verwendung von sGC-Stimulatoren, sGC-Aktivatoren, alleine und in Kombination mit PDE5-Hemmern zur Behandlung von systemischer Sklerose (SSc) |
EP3024455A1 (de) | 2013-07-25 | 2016-06-01 | Bayer Pharma Aktiengesellschaft | Sgc-stimulatoren oder sgc-aktivatoren und pde5-inhibitoren in kombination mit einer zusatzbehandlung zur behandlung von zystischer fibrose |
CN107580495A (zh) * | 2015-05-06 | 2018-01-12 | 拜耳制药股份公司 | 单独和与PDE5抑制剂组合的sGC刺激剂、sGC活化剂用于治疗伴随系统性硬化症(SSc)的指溃疡(DU)的用途 |
WO2022032141A1 (en) * | 2020-08-07 | 2022-02-10 | Eicos Sciences, Inc. | Method of treating systemic sclerosis with symptomatic raynaud's phenomenon by intravenous or subcutaneous iloprost administration |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000002851A1 (en) * | 1998-07-08 | 2000-01-20 | Aventis Pharma Deutschland Gmbh | Sulfur substituted sulfonylaminocarboxylic acid n-arylamides, their preparation, their use and pharmaceutical preparations comprising them |
WO2000006569A1 (de) * | 1998-07-29 | 2000-02-10 | Bayer Aktiengesellschaft | Mit sechsgliedrigen heterocyclischen ringen kondensierte substituierte pyrazolderivate |
WO2000027394A1 (en) * | 1998-11-05 | 2000-05-18 | University College London | Activators of soluble guanylate cyclase |
WO2001019780A2 (de) * | 1999-09-13 | 2001-03-22 | Bayer Aktiengesellschaft | Neuartige aminodicarbonsäurederivate mit pharmazeutischen eigenschaften |
WO2001032604A1 (en) * | 1999-11-05 | 2001-05-10 | University College London | Activators of soluble guanylate cyclase |
WO2002042301A1 (de) * | 2000-11-22 | 2002-05-30 | Bayer Aktiengesellschaft | Neue pyridin-substituierte pyrazolopyridinderivate |
WO2003095451A1 (de) * | 2002-05-08 | 2003-11-20 | Bayer Healthcare Ag | Carbamat-substituierte pyrazolopyridine |
-
2005
- 2005-10-06 DE DE102005047945A patent/DE102005047945A1/de not_active Withdrawn
-
2006
- 2006-07-04 US US11/988,991 patent/US20090215769A1/en not_active Abandoned
- 2006-07-04 CA CA002615051A patent/CA2615051A1/en not_active Abandoned
- 2006-07-04 WO PCT/EP2006/006501 patent/WO2007009589A2/de active Application Filing
- 2006-07-04 JP JP2008521831A patent/JP2009501737A/ja active Pending
- 2006-07-04 EP EP06762392A patent/EP1917008A2/de not_active Withdrawn
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000002851A1 (en) * | 1998-07-08 | 2000-01-20 | Aventis Pharma Deutschland Gmbh | Sulfur substituted sulfonylaminocarboxylic acid n-arylamides, their preparation, their use and pharmaceutical preparations comprising them |
WO2000006569A1 (de) * | 1998-07-29 | 2000-02-10 | Bayer Aktiengesellschaft | Mit sechsgliedrigen heterocyclischen ringen kondensierte substituierte pyrazolderivate |
WO2000027394A1 (en) * | 1998-11-05 | 2000-05-18 | University College London | Activators of soluble guanylate cyclase |
WO2001019780A2 (de) * | 1999-09-13 | 2001-03-22 | Bayer Aktiengesellschaft | Neuartige aminodicarbonsäurederivate mit pharmazeutischen eigenschaften |
WO2001032604A1 (en) * | 1999-11-05 | 2001-05-10 | University College London | Activators of soluble guanylate cyclase |
WO2002042301A1 (de) * | 2000-11-22 | 2002-05-30 | Bayer Aktiengesellschaft | Neue pyridin-substituierte pyrazolopyridinderivate |
WO2003095451A1 (de) * | 2002-05-08 | 2003-11-20 | Bayer Healthcare Ag | Carbamat-substituierte pyrazolopyridine |
Also Published As
Publication number | Publication date |
---|---|
CA2615051A1 (en) | 2007-01-25 |
JP2009501737A (ja) | 2009-01-22 |
EP1917008A2 (de) | 2008-05-07 |
WO2007009589A3 (de) | 2007-08-16 |
DE102005047945A1 (de) | 2007-01-18 |
US20090215769A1 (en) | 2009-08-27 |
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