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WO1993018767A1 - Utilisation de sydnonimines pour traiter les troubles de l'erection - Google Patents

Utilisation de sydnonimines pour traiter les troubles de l'erection Download PDF

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Publication number
WO1993018767A1
WO1993018767A1 PCT/EP1993/000546 EP9300546W WO9318767A1 WO 1993018767 A1 WO1993018767 A1 WO 1993018767A1 EP 9300546 W EP9300546 W EP 9300546W WO 9318767 A1 WO9318767 A1 WO 9318767A1
Authority
WO
WIPO (PCT)
Prior art keywords
sydnonimine
methyl
carbonyl
dimethyl
amino
Prior art date
Application number
PCT/EP1993/000546
Other languages
German (de)
English (en)
Inventor
Karl Schönafinger
Eckard Kujath
Christian Stief
Original Assignee
Cassella Aktiengesellschaft
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 DE19924209462 external-priority patent/DE4209462A1/de
Priority claimed from DE19924213338 external-priority patent/DE4213338A1/de
Application filed by Cassella Aktiengesellschaft filed Critical Cassella Aktiengesellschaft
Publication of WO1993018767A1 publication Critical patent/WO1993018767A1/fr

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
    • A61K31/495—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
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • 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
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame

Definitions

  • the present invention relates to the use of svdnonimines and pharmacologically acceptable salts thereof for the treatment of erectile dysfunctions.
  • vasoactive substances such as yohimbine, phenoxybenzamine, terbutaline, Bethanechol, levodopa, verapamil or theophylline has proven unsuccessful.
  • vasoactive substances such as yohimbine, phenoxybenzamine, terbutaline, Bethanechol, levodopa, verapamil or theophylline has proven unsuccessful.
  • prosthetic implants or revascular An intracavernous injection of papaverine (Virag, Lancet, 2, 938, 1982), the ⁇ -receptor blocker phenoxybenzamine (Brindley, Br. J. Psychiatr., 143, 332, 1983) and a combination of papaverine and the - ⁇ -receptor blocker phentolamine (Stief, Urologe A, 25, 63, 1986) as successful.
  • the latter therapy method can be carried out independently by the patient and is also referred to as erectile tissue auto-injection therapy (SKAT).
  • acetylcholine is associated with strong systemic side effects in the case of a short-term erection and the injection of prostaglandin E ⁇ is rejected by the patients because of excessive pain.
  • the object of the invention was therefore the development and manufacture of medicaments for the treatment of neurogenic, arterial, neurotransmitter-related, myopathic, venous or psychogenic erectile dysfunctions without the side effects mentioned. Surprisingly, it has now been found that this problem can be solved by Sydnonimine.
  • Sydnonimines are compounds whose pharmacology has been known for a long time (Chemistry in our time, 13th year, page 51 (1984)), and besides the vasodilating effects, the antithrombotic effects are also described (J. Cardiovasc. Pharmacol. 1989 , 14 (Suppl. 11), page 129). Sydnonimines to the cardiovascular-Sys ⁇ tems are used as a means of preventing a nd treatment of diseases and as such commercially.
  • the present invention thus relates to the use of sydnonimines of the general formula I.
  • R is an amino group of the formula
  • R ' is hydrogen, halogen, alkyl, cycloalkyl, arylalkyl,
  • alkyl alkenyl, cycloalkyl, bicycloalkyl, tricycloalkyl, alkyl-X-alkyl, arylalkyl, which also by
  • Alkyl or halogen can be substituted, hydroxyalkyl, a heterocyclic ring bound via an alkylene chain or a radical
  • R represents hydrogen or one of the meanings of R has 4 ;
  • R 6 represents alkyl
  • R 7 aryl, by 1 to 3 halogen atoms and / or 1 to 3 alkyl radicals and / or 1 to 3 alkoxy radicals and / or 1 or 2 nitro groups mono-, di- or tri-substituted aryl radical, arylalkenyl, tricycloalkyl, bicycloalkoxy, tricycloalkoxy , Aryloxy, alkoxycarbonyl, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazinyl,
  • X is NR 4 , NS0 2 R 8 , NC0 2 alkyl, S (0) n , 0, (CH 2 ) m or a simple bond; n is 0, 1 or 2; m is 1, 2 or 3; and o R denotes alkyl, aryl, alkylaryl, haloaryl or dialkyl-a ino, where the aryl groups can also be substituted by alkyl or halogen, for the treatment of erectile dysfunctions, where X cannot be 0 if R 2 and R 3 are hydrogen .
  • Alkyl residues and alkenyl residues can be straight-chain or branched and preferably have 1 to 6 C atoms, particularly preferably 1 to 4 C atoms. This also applies if they are in connection with other groups, e.g. B. as alkoxy, arylalkyl, etc. are present.
  • alkyl radicals are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl and tert-butyl.
  • Cycloalkyl preferably has 5 to 7 carbon atoms and particularly preferably denotes cyclopentyl and cyclohexyl.
  • Bicycloalkyl preferably has 7 to 14 carbon atoms. Tricycloalkyl preferably has 7 to 16 carbon atoms.
  • Halogen preferably means fluorine, chlorine, bromine or iodine.
  • Aryl preferably has 6 to 10 carbon atoms and particularly preferably means ⁇ - or ⁇ -naphthyl or phenyl.
  • Arylalkyl is preferably benzyl and phenylethyl.
  • Aryl-O-alkyl is preferably phenoxymethyl and phenoxyethyl. The same applies to aryl-S-alkyl.
  • aryl radicals which stand for R can be mono-, di- or tri-substituted, although only a maximum of 2 nitro groups, such as 2-methyl-4,6-dinitrophenyl and 2-chloro-6-, can be present even when trisubstituted. methyl-4-nitrophenyl.
  • Halogen substituents for the aryl radicals are, for example Chlorine and bromine atoms in loading
  • Preferred radicals R are piperidino, pyrrolidino, dimethylamino, diethylamino, diisopropylamino, tert.butylmethylamino, tert.butylethylamino, tert.butylpropylamino, ter .butylbutylamino, tert.butyl-hydroxyethylamino, dibenzylamino, 2-carboxy-pyrrolidino, 2-carboxy-piperidino, 4-carboxypiperidino, dicyclohexylamino, N-methylpiperazino, 2,2-dimethylpiperidino, 3,3-dimethyl-morpholino, 3,3-dimethylthiomorpholino, 3,3-dimethyl-
  • Preferred radicals R 2 are hydrogen, methyl, ethyl, propyl, isopropyl and butyl, with hydrogen being particularly preferred.
  • Preferred radicals R 3 are hydrogen, formyl, acetyl,
  • Propionyl, butyryl, isobutyryl, pivaloyl, benzoyl, anisoyl, hydrogen is particularly preferred.
  • N N'-dicarboxy-3,3'-diphenyl-4,4'-bisydnonimine
  • N N'-dicarboxy-3,3'-dimethyl-4,4'-bisydnonimine
  • N-Benzoyl-3 - (((2-carboxy-3- (hydroxymethyl) -8-oxo-5-thia-1-azabicyclo (4.2.0) oct-2-en-7-yl) carbamoyl) methyl) - syd ⁇ nonimin acetate; 3 - (((2-Carboxy-3- (hydroxymethyl) -8-oxo-5-thia-l-azabicyclo (4.2.0) oct-2-en-7-yl) carbamoyl) methyl) -N- (methylcarbamoyl) -sydnonimine acetate; 3-sec-octyl-sydnonimine;
  • N-carboxy-3- (p-chlorophenyl) sydnonimine methyl ester N-carboxy-3- ⁇ -tolyl-sydnonimine methyl ester;
  • Pharmacologically acceptable salts of the sydnonimines of the general formula I are in particular acid addition salts with inorganic or organic acids.
  • Suitable acids are, for example, hydrogen chloride, hydrogen bromide, naphthalenedisulfonic acids, in particular naphthalene disulfonic acid (1,5), phosphoric, nitric, sulfuric, oxalic, milk, wine, vinegar, salicylic, benzoic , Ants, propion, pivaline, diethyl vinegar, malon, amber, pimelin, fumar, malein, apple, sulfamine, phenylpropion, glucon, ascorbin, isonicotine, Methane sulfonic, p-toluenesulfonic, citric or adipic acid.
  • the hydrochlorides are particularly preferred.
  • Sydnonimine in a pharmaceutical preparation.
  • parenteral and topical forms of application such as lotions, creams, solutions, gels, sprays, elastic liquid plasters, transdermal systems or coatings for condoms in question.
  • Parenteral administration is preferred, since it is the safest form of using a targeted amount of active ingredient directly without further adulteration by other factors.
  • Preparations for parenteral administration contain 0.1 to 5 mg, preferably 0.1 to 2 mg of sydnonimine of the general formula I per dose unit and can be given in separate
  • Dosage unit forms such as B. ampoules or vials. Solutions of the active ingredient are preferably used, preferably aqueous solutions and above all isotonic solutions, but also suspensions. These injection forms can be made available as a ready-to-use preparation or only directly before use by mixing the active compound, eg. B. the lyophilizate, optionally with other solid carriers, with the desired solvent or suspending agent. For topical forms of application, a higher active substance concentration than that mentioned for parenteral preparations is of course indicated.
  • Parenteral and topical forms can be sterilized and / or optionally contain auxiliaries such as preservatives, stabilizers, wetting agents, penetrants, emulsifiers, spreading agents, solubilizers, salts for regulating the osmotic pressure or for buffering and / or viscosity regulators.
  • auxiliaries such as preservatives, stabilizers, wetting agents, penetrants, emulsifiers, spreading agents, solubilizers, salts for regulating the osmotic pressure or for buffering and / or viscosity regulators.
  • Such additives are e.g. B. tartrate and citrate buffers, ethanol, complexing agents (such as ethylenediamine-tetraacetic acid and its non-toxic salts).
  • High-molecular polymers such as liquid polyethylene oxide, carboxymethyl- cellulosic, polyvinylpyrrolidones, dextrans or gelatin.
  • Solid carriers are e.g. B. starch, lactose, mannitol, methyl cellulose, talc, highly disperse silicas, higher molecular weight fatty acids (such as stearic acid), gelatin, agar, calcium phosphate, magnesium stearate, animal and vegetable fats, solid high molecular weight polymers, such as polyethylene glycol.
  • Oily suspensions for parenteral or topical applications can be vegetable synthetic or semisynthetic oils such as liquid fatty acid esters with 8 to 22 carbon atoms in the fatty acid chains, e.g. B. palmitic, lauric, tridecyl, margarine, stearic, araquinic, myristic, behenic, pentadecyl, linoleic, elaidic, brasidic, erucic or oleic acid, with a-bis trivalent alcohols with 1 to 6 carbon atoms, such as, for example, methanol, ethanol, propanol, butanol, pentanol or their isomers, glycol or glycerol, have been esterified.
  • vegetable synthetic or semisynthetic oils such as liquid fatty acid esters with 8 to 22 carbon atoms in the fatty acid chains, e.g. B. palmitic, lauric, tridecyl, margarine, ste
  • Such fatty acid esters are, for example, commercially available miglyols, isopropyl myristate, isopropyl palmitate, isopropyl stearate, PEG 6-capric acid, cypryl / capric acid esters of saturated fatty alcohols, polyoxyethylene glycerol trioleates, ethyl oleate, wax-like fatty acid esters such as artificial duck fatty acid, ethyl ester fatty acid, coconut oil fatty acid, coconut oil ester, isol fatty acid ester, isol fatty acid ethyl ester, isol fatty acid ethyl ester, isol fatty acid ethyl ester, isol fatty acid ethyl ester, isol fatty acid ethyl ester, isol fatty acid ethyl ester, isol fatty acid ethyl ester, isopropyl fatty acid ethy
  • silicone oils of various viscosities or fatty alcohols such as isotidexyl alcohol, 2-octyldodecanol, cetylstearyl alcohol or oleyl alcohol, fatty acids such as oleic acid.
  • Vegetable oils such as castor oil, almond oil, olive oil, sesame oil, cottonseed oil, peanut oil or soybean oil can also be used.
  • the substances mentioned also have the properties of a spreading agent, ie there is a particularly good distribution on the skin.
  • Suitable solvents, gel formers and solubilizers are water or water-miscible solvents. Are suitable for. B.
  • alcohols such as ethanol or isopropyl alcohol, benzyl alcohol, 2-0ctyl-dodecanol, polyethylene glycols, phthalates, adipates, propylene glycol, glycerol, di- or tripropylene glycol, waxes, methyl cellosolve, cellosolve, ester, morpholines, dioxane, dimethyl sulfoxide, dimethylformamide, Tetrahydrofuran, cyclohexanone etc.
  • alcohols such as ethanol or isopropyl alcohol, benzyl alcohol, 2-0ctyl-dodecanol, polyethylene glycols, phthalates, adipates, propylene glycol, glycerol, di- or tripropylene glycol, waxes, methyl cellosolve, cellosolve, ester, morpholines, dioxane, dimethyl sulfoxide, dimethylformamide, Tetrahydrofuran,
  • Cellulose ethers which dissolve or swell both in water and in organic solvents and which form a type of film after drying, such as, for example, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose or soluble starches, can be used as film formers.
  • Ionic macromolecules in particular are used here, such as sodium carboxymethyl cellulose, polyacrylic acid, polymethacrylic acid and its salts, sodium amylopectin semiglycolate, alginic acid or propylene glycol alginate as sodium salt, gum arabic, xanthan gum, guar gum or carrageenan.
  • auxiliaries that can be used are: glycerol, paraffin of different viscosities, triethanolamine, collagen, allantoin, novantisol acid, perfume oils.
  • surfactants such as, for example, sodium lauryl sulfate, fatty alcohol ether sulfates, di-Na-N-lauryl- ⁇ -iminodipropionate, polyoxyethylated castor oil or sorbitan monooleate, sorbitan monostearate, cetylal - alcohol, lecithin, glycerol monostearate, polyoxyethylene stearate, alkylphenol polyglycol ether, cetyltrimethylammonium chloride or mono- / dialkylpolyglycol ether-orthophosphoric acid-monoethanolamine salts.
  • surfactants such as, for example, sodium lauryl sulfate, fatty alcohol ether sulfates, di-Na-N-lauryl- ⁇ -iminodipropionate, polyoxyethylated castor oil or sorbitan monooleate, sorbitan monostearate, cetylal - alcohol,
  • Stabilizers such as montmorillonites or colloidal silicas for stabilizing emulsions or for preventing the breakdown of active substances such as antioxidants, for example tocopherols or butylhydroxyanisole, or preservatives such as p-hydroxybenzoic acid esters can also be used to prepare the ge ⁇ desired formulations may be required.
  • Formulations preferably organic solvents which are well tolerated by the skin, such as ethanol, methylpyrrolidone, polyethylene glycol, oleyl alcohol, octanol, linoleic acid, triacetine, propylene glycol, glycerol, solketal or dimethyl sulfoxide.
  • organic solvents such as ethanol, methylpyrrolidone, polyethylene glycol, oleyl alcohol, octanol, linoleic acid, triacetine, propylene glycol, glycerol, solketal or dimethyl sulfoxide.
  • Compounds such as quinolines, for example 8-hydroxyquinoline or quinoline yellow, are suitable as photostabilizers; suitable food colors; Flavanoids such as B. hesperidin, hesperidin-methylchalcon, hesperidin phosphate, hesperitin, quercetin, quercitrin, rutin, rutin sulfate, naringenin, camphor oil, kaempferol 7,4'-dimethyl ether, morin, apigetrin, luteolin and its 7-glycoside, or Troxerutin. They are added in a quantity ratio of 0.001: 1 to 50: 1, preferably 0.1: 1 to 20: 1.
  • the preparation, filling and sealing of the preparations is carried out under the usual antimicrobial and aseptic conditions.
  • packaging is also possible in separate dose units to facilitate handling, here too, as in parenteral forms, if necessary for reasons of stability, by separate packaging of the active substances or their combinations as lyophilisate, if appropriate with solid carriers, and the necessary solvents etc.
  • the sydnonimines of the general formula I are used in combination with one or more synergistically active substances.
  • synergistic substances are, for example, adenosine, vitamins, e.g. B. Vitamin A or H, prostaglandins, e.g. B. E ⁇ , peptides such. B.
  • Citricone gene related peptides CGRP
  • calcium antagonists such as nifedipine, verapamil, diltiaze, gallopamil, niludipine, nimodipine, nicardipine, prenylamine, fendiline, terodiline, nisaldipine, nitrendipine or perhexiline, for example ⁇ -receptor blockers Phentolamine methanesulfonate, phenoxybenzamine or minoxidil, smooth muscle relaxants such as papaverine, trinitroglycerin, sodium nitroprusside or S-nitroso-N-acetylpenicillamine.
  • Particularly advantageous and also an object of the present invention is a disposable medicament package containing in sterile packaging a disposable syringe with a parenteral preparation of a sydnonimine of the general formula I, optionally in combination with a synergistically active substance; with disinfectant provided sterile swabs as well as usage information.
  • the disposable pre-filled syringes mentioned are preferably of the ultrafine type, as are used, for example, in insulin therapy. Syringes of the type of auto-injectors that are even easier to handle are also preferred.
  • the pre-filled syringes are preferably made in opaque form, since this adds photostabilizers to the parenteral ones
  • Preparations are unnecessary. However, they can also be designed in such a way that the active ingredient and associated injection solvent are only mixed directly before the injection. This can e.g. B. happen in two-container ampoules or syringes. As a result, any photostabilizer additive that may be required can also be omitted.
  • the sterile swabs for disinfection contain the usual skin disinfectants such as ethanol. However, they can also contain erection-promoting agents in a topically applicable form to increase or prolong the action.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation de sydnonimines de la formule générale (I) selon la revendication principale, ainsi que de leurs sels compatibles sur le plan pharmacologique, pour traiter les troubles de l'érection.
PCT/EP1993/000546 1992-03-24 1993-03-10 Utilisation de sydnonimines pour traiter les troubles de l'erection WO1993018767A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19924209462 DE4209462A1 (de) 1992-03-24 1992-03-24 Verwendung von Sydnoniminen zur Behandlung erektiler Dysfunktionen
DEP4209462.3 1992-03-24
DE19924213338 DE4213338A1 (de) 1992-04-23 1992-04-23 Sydnonimine zur Behandlung erektiler Dysfunktionen
DEP4213338.6 1992-04-23

Publications (1)

Publication Number Publication Date
WO1993018767A1 true WO1993018767A1 (fr) 1993-09-30

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1993/000546 WO1993018767A1 (fr) 1992-03-24 1993-03-10 Utilisation de sydnonimines pour traiter les troubles de l'erection

Country Status (2)

Country Link
AU (1) AU3632393A (fr)
WO (1) WO1993018767A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018966A1 (fr) * 1993-02-26 1994-09-01 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Systeme therapeutique transdermique substances actives representant des sources d'oxyde d'azote
GB2339533A (en) * 1998-07-14 2000-02-02 James Martin Biggs Topical pharmaceutical preparations
WO2014145126A3 (fr) * 2013-03-15 2014-12-18 Melior Discovery, Inc. Méthodes de traitement de la dyskinésie et de troubles associés

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1620501A1 (de) * 1964-06-08 1970-04-16 Takeda Chemical Industries Ltd Neue Sydnonimin-Derivate und Verfahren zu ihrer Herstellung
DE1670127A1 (de) * 1966-08-09 1970-12-03 Boehringer Sohn Ingelheim Verfahren zur Herstellung neuer substituierter 3-Amino-sydnonimine
DE1695897A1 (de) * 1966-07-04 1972-02-03 Takeda Chemical Industries Ltd N-Acyl-sydnonimin-Derivate
EP0276710A1 (fr) * 1987-01-24 1988-08-03 CASSELLA Aktiengesellschaft Allylmercaptoacétylsydnonimines, procédé pour leur préparation et leur application

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1620501A1 (de) * 1964-06-08 1970-04-16 Takeda Chemical Industries Ltd Neue Sydnonimin-Derivate und Verfahren zu ihrer Herstellung
DE1695897A1 (de) * 1966-07-04 1972-02-03 Takeda Chemical Industries Ltd N-Acyl-sydnonimin-Derivate
DE1670127A1 (de) * 1966-08-09 1970-12-03 Boehringer Sohn Ingelheim Verfahren zur Herstellung neuer substituierter 3-Amino-sydnonimine
EP0276710A1 (fr) * 1987-01-24 1988-08-03 CASSELLA Aktiengesellschaft Allylmercaptoacétylsydnonimines, procédé pour leur préparation et leur application

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BLOOD VESSELS Bd. 27, 1990, Seiten 282 - 294 'Molsidomine' *
Derwent Publications Ltd., London, GB; AN 90-286014 *
WORLD J.UROL. Bd. 9, 1991, Seiten 237 - 239 'Preliminary Report on the Effect of the Nitric Oxide Donor SIN-1 on the Human Cavernous Tissue in vivo' *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018966A1 (fr) * 1993-02-26 1994-09-01 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Systeme therapeutique transdermique substances actives representant des sources d'oxyde d'azote
GB2339533A (en) * 1998-07-14 2000-02-02 James Martin Biggs Topical pharmaceutical preparations
WO2014145126A3 (fr) * 2013-03-15 2014-12-18 Melior Discovery, Inc. Méthodes de traitement de la dyskinésie et de troubles associés
US9051312B2 (en) 2013-03-15 2015-06-09 Melior Discovery, Inc. Methods of treating dyskinesia and related disorders
CN105209445A (zh) * 2013-03-15 2015-12-30 梅利奥尔探索公司 治疗运动障碍和相关病症的方法
US9402830B2 (en) 2013-03-15 2016-08-02 Melior Discovery, Inc. Methods of treating dyskinesia and related disorders
US10188651B2 (en) 2013-03-15 2019-01-29 Melior Pharmaceuticals Ii, Llc Methods of treating sleep disorders
EA032064B1 (ru) * 2013-03-15 2019-04-30 Мелиор Фармасьютикалз Ii, Ллс Способ лечения леводопа-индуцированной дискинезии с применением сиднокарба
US11351169B2 (en) 2013-03-15 2022-06-07 Melior Pharmaceuticals Ii, Llc Methods of treating dyskinesia and related disorders
US12048697B2 (en) 2013-03-15 2024-07-30 Melior Pharmaceuticals Ii, Llc Methods of treating dyskinesia and related disorders

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Publication number Publication date
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