EP1917008A2 - Use of soluble guanylate cyclase for the treatment of raynaud's phenomenon - Google Patents
Use of soluble guanylate cyclase for the treatment of raynaud's phenomenonInfo
- Publication number
- EP1917008A2 EP1917008A2 EP06762392A EP06762392A EP1917008A2 EP 1917008 A2 EP1917008 A2 EP 1917008A2 EP 06762392 A EP06762392 A EP 06762392A EP 06762392 A EP06762392 A EP 06762392A EP 1917008 A2 EP1917008 A2 EP 1917008A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- treatment
- raynaud
- phenomenon
- medicament
- guanylate cyclase
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
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.
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102005033370 | 2005-07-16 | ||
DE102005047945A DE102005047945A1 (en) | 2005-07-16 | 2005-10-06 | Use of soluble guanylate cyclase activators for the treatment of Raynaud's phenomena |
PCT/EP2006/006501 WO2007009589A2 (en) | 2005-07-16 | 2006-07-04 | Use of soluble guanylate cyclase for the treatment of raynaud's phenomenon |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1917008A2 true EP1917008A2 (en) | 2008-05-07 |
Family
ID=37563587
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP06762392A Withdrawn EP1917008A2 (en) | 2005-07-16 | 2006-07-04 | Use of soluble guanylate cyclase for the treatment of raynaud's phenomenon |
Country Status (6)
Country | Link |
---|---|
US (1) | US20090215769A1 (en) |
EP (1) | EP1917008A2 (en) |
JP (1) | JP2009501737A (en) |
CA (1) | CA2615051A1 (en) |
DE (1) | DE102005047945A1 (en) |
WO (1) | WO2007009589A2 (en) |
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 |
NZ603799A (en) * | 2010-05-26 | 2014-10-31 | Bayer Ip Gmbh | The use of sgc stimulators, sgc activators, alone and combinations with pde5 inhibitors for the treatment of systemic sclerosis (ssc). |
DE102010021637A1 (en) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituted 5-fluoro-1H-pyrazolopyridines and their use |
EP2594270A3 (en) * | 2011-11-18 | 2013-07-31 | BIP Patents | The use of sGC stimulators, sGC activators, alone and combinations with PDE5 inhibitors for the treatment of systemic sclerosis (SSc) |
EP3024455A1 (en) | 2013-07-25 | 2016-06-01 | Bayer Pharma Aktiengesellschaft | Sgc stimulators or sgc activators and pde5 inhibitors in combination with additional treatment for the therapy of cystic fibrosis |
EP3291811B1 (en) * | 2015-05-06 | 2019-08-07 | Bayer Pharma Aktiengesellschaft | The use of sgc stimulators, sgc activators, alone and combinations with pde5 inhibitors for the treatment of digital ulcers (du) concomitant to systemic sclerosis (ssc) |
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 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CZ302691B6 (en) * | 1998-07-08 | 2011-09-07 | Sanofi - Aventis Deutschland GmbH | N-arylamide compound, process for its preparation, pharmaceutical composition containing thereof, the compound for use as activator and for use in therapy or prophylaxis |
DE19834044A1 (en) * | 1998-07-29 | 2000-02-03 | Bayer Ag | New substituted pyrazole derivatives |
GB9824310D0 (en) * | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
DE19943635A1 (en) * | 1999-09-13 | 2001-03-15 | Bayer Ag | Novel aminodicarboxylic acid derivatives with pharmaceutical properties |
CA2389773A1 (en) * | 1999-11-05 | 2001-05-10 | Robert Glen | Activators of soluble guanylate cyclase |
AR031176A1 (en) * | 2000-11-22 | 2003-09-10 | Bayer Ag | NEW DERIVATIVES OF PIRAZOLPIRIDINA SUBSTITUTED WITH PIRIDINE |
DE10220570A1 (en) * | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamate-substituted pyrazolopyridines |
-
2005
- 2005-10-06 DE DE102005047945A patent/DE102005047945A1/en not_active Withdrawn
-
2006
- 2006-07-04 US US11/988,991 patent/US20090215769A1/en not_active Abandoned
- 2006-07-04 WO PCT/EP2006/006501 patent/WO2007009589A2/en active Application Filing
- 2006-07-04 EP EP06762392A patent/EP1917008A2/en not_active Withdrawn
- 2006-07-04 JP JP2008521831A patent/JP2009501737A/en active Pending
- 2006-07-04 CA CA002615051A patent/CA2615051A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO2007009589A2 * |
Also Published As
Publication number | Publication date |
---|---|
CA2615051A1 (en) | 2007-01-25 |
US20090215769A1 (en) | 2009-08-27 |
WO2007009589A3 (en) | 2007-08-16 |
DE102005047945A1 (en) | 2007-01-18 |
WO2007009589A2 (en) | 2007-01-25 |
JP2009501737A (en) | 2009-01-22 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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17P | Request for examination filed |
Effective date: 20080218 |
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AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
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RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BAYER SCHERING PHARMA AG |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT |
|
17Q | First examination report despatched |
Effective date: 20100715 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BAYER PHARMA AKTIENGESELLSCHAFT |
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DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 20130201 |