IL28432A - Substituted 3-amino-sydnonimines and processes for their manufacture - Google Patents

Substituted 3-amino-sydnonimines and processes for their manufacture

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Publication number
IL28432A
IL28432A IL6728432A IL2843267A IL28432A IL 28432 A IL28432 A IL 28432A IL 6728432 A IL6728432 A IL 6728432A IL 2843267 A IL2843267 A IL 2843267A IL 28432 A IL28432 A IL 28432A
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Israel
Prior art keywords
sydnonimine
amino
mol
hydrochloride
added
Prior art date
Application number
IL6728432A
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Hebrew (he)
Original Assignee
Boehringer Sohn Ingelheim
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Publication date
Application filed by Boehringer Sohn Ingelheim filed Critical Boehringer Sohn Ingelheim
Publication of IL28432A publication Critical patent/IL28432A/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/04—1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical 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)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Description

28432/3 The present invention relates tb .new substituted 3-amino-sydnonimines having valuable pharmacological properties.
According to the present invention we provide compounds of the general formula: .' , ■ , wherein ^ and:R2, which may be identical or different ,' represent:; alkyl, mono- or polyhaloalkyl^ alkenyl, · alkynyl or. phenylalkyl groups, (which latter groups may be substituted in the phenyl ring with one or more halogen atoms or alkyl radicals a or methylenedioxy radical) or a piperidinylmethyl radical or R1 .' and R^, together with the. ad jacent nitrogen atom, represent a heterocyclic ring system which may contain one or more further hetero atoms and may be substituted by at least, one . lower alkyl, carobylic acyl or phenyl group; represents hydrogen, or an alkyl or phenylalkyl group; ^ represents hydrogen or the grou R^CO- where R,- represents an alkyl, cycloalkyl or alkoxy radical or .a phenyl radical which may be. substituted with chlorine or methyl, or a phenylalkyl, 5-nitrofuryl. or. pyridyl radical; and . acid addition salts thereof, for example, hydrohalides , hydrosulphates and hydronitrates In the case where salts of formula 1 are to he used directly as medicines, such salts must of course he non-toxic acid addition salts "by which term we mean those salts, the anionic moieties of which are physiologically compatible in the dosages at which the salts are administered. Non toxic salts may be formed from other salts by conventional ion-exchange methods.
According to a further feature of the invention, we provide a process for the preparation of compounds of formula I (as hereinbefore defined) which comprises reacting a compound of formula Εη NO CN (wherein R^, R2 and R^ are as hereinbefore defined) with an agent serving to effect the cyclisation of said nitroso compound to form a compound of formula I in which R^ = H, which compound is, if desired, reacted with an acylating agent serving to introduce the R5CO- group (where R^ is. as defined herein) at the 6-position.
The cyclisation of a compound of formula II according to the invention can be effected with the aid of conventional condensing agents, such as strong The reaction can be carried out either in the presence or absence of solvents. Methanol, ethanol, acetone, chloroform, tetrahydrofuran and water are par-r ticularly preferred for use as solvents. The reaction can be effected at moderately elevated temperatures, ambient temperature or under cooling.
To obtain compounds of formula I which are acylated at the 6 nitrogen atom, the compounds of general formula I, wherein R^ represents hydrogen, obtained according to the above-described process, may be acylated at the imino nitrogen atom by any convenient method, for example, by treatment with the corresponding acid halide or anhydride, such as acetic anhydride, benzoyl chloride or nicotinoyl chloride, or by reaction with the corresponding halogeno-formic acid ester, for example, methyl or ethyl chloro-formate. This reaction is preferably carried out in the presence of an acid-acceptor, for example an organic or inorganic base, such as pyridine, or an alkali metal carbonate or acetate, if desired, in the presence of a solvent.
The compounds of formula I in the free-base may often be unstable and are hence preferably isolated in the form of an acid addition salt thereof. Such compounds in which R^ is a group R^CO- may however be sufficiently stable to be isolated and used in the free-base form. Acid addition salts may be formed with inorganic or organic acids.
Preferred inorganic acids for the preparation of The following compounds may for example be used as starting materials: N-nitroso-(dimethylamino)-ramino-acetonitrile ; N-nitroso-(morpholino)-amino-acetonitrile; N-nitroso-(metliyl-plienylethylamino)~amino-aGetonitrile; N-nitroso-(methyl-2-piperidinylmethylamino)-amino- acetonitrile; N-nitroso-met^l-a-methylbenzylamino)-amino-acetonitrile ; N-nitroso-(2-phenylpiperidino)-amino-acetonitrile ; N-nitroso-(dibenzylamino) amino-acetonitrile ; N-nitroso-(methyl-propargylamino)-amino-acetonitrile; N-nitroso-(methyl-benzylamino)-amino-acetonitrile; N-nitroso-(diallylamino)-amino-acetonitrile ; N-nitroso-(hexamethyleneimino)-amino-acetonitrile; N-nitroso-C^-methylpiperazinyl-l1)-amino-acetonitrile; N-nitroso-(l,2,3, -tetrahydroisoquinolinyl)-amino- acetonitrile; N-nitroso-(piperidino)-amino-acetonitrile ; N-nitroso-(diallylamino)-a-pbenylethyl-amino-acetonitrile; N-nitroso-(diallylamino)-a-methyl-amino-acetonitrile; N-nitroso-(diallylamino)-a-ethyl-amino-acetonitrile; N-nitroso-(pyrrolidino)-amino-acetonitrile , As mentioned above, the substituted 3-amino-sydnonimines and their acid addition salts according to the invention have valuable pharmacological properties. The compounds according to the invention lower the blood pressure for particularly long periods even when administered in small doses and also display an action on the invention, we provide pharmaceutical compositions comprising, as active ingredient, at least one compound of formula I (as hereinbefore defined) or a non-toxic acid addition salt thereof in association with a pharmaceutical carrier or excipient.
The compositions may be presented in a form suitable for enteral, e.g. oral, or parenteral administration. Thus, for example, compositions for oral administration may be solid or liquid and may take the form of granules, tablets, dragees, pills, coated tablets, capsules, syrups, emulsions, solutions, suspensions or drops, such compositions comprising carriers or excipients conventionally used in the pharmaceutical art.
The compositions may thus include fillers, extenders, binders, disintegrating agents, lubricants, thickeners, diluents, solvents, solubility-promoters, agents for achieving a depot-effect, emulsifiers or buffer substances. For example, suitable tabletting excipients include lactose, potato and soluble starches and magnesium stearate.
For parenteral administration, the carrier may be a sterile, parenterally acceptable liquid such as sterile water, or a parenterally acceptable oil e.g. arachis oil, contained in ampoules or multi-dose flasks. Compositions for rectal administration may take the form of suppositories, the carrier comprising a suppository base. tablets, capsules and ampoules are examples of suitable dosage unit forms. Each dosage unit preferably contains 10 to 100 mg, and especially 20 to 50 mg, of active ingredient.
The compositions according to the invention may, if desired, also contain a further therapeutic compound, e.g. a compound having a saluretic activity.
The following examples Illustrate the invention.
Example 1 3-Piperidino«-sydnonimine To a mixture consisting of 95 g (0.95 moi) N-amino-piperidine and 100 ml water, 80 ml of concentrated hydrochloric acid were added at 10°0 slowly with stirring, so that the pH was approximately neutral. The mixture was then cooled to 5°C in the ice bath and in the course of 30 minutes a solution of 61.5 g (0.95 mol) potassium cyanide in 130 ml water was added thereto. The temperature was maintained at 10°C and in the course of further 30 minutes 7I .5 ml of a 40% formaldehyde solution (0.95 mol) were added. The mixture was stirred for one hour, then brought to room temperature and stirred for another hour. The mixture was then again cooled, to 5°C and 40 ml of concentrated hydrochloric acid and a solution of 69 g (1 mol) sodium nitrite in 140 ml of water were added. The pH of the solution was maintained at an acid value by gradual addition of 40 ml hydrochloric acid. .
The nitroso-derivative thus formed was extracted with chloroform; the crude yield was 160 g. The crude product was then gradually introduced while stirring and cooling into one litre of methanolic hydrochloric acid. was effected with chloroform containing 20% methanol, to yield 106,2 g (53% of theory) of 3-piperidino-sydnonimine hydrochloride. After recrystallization from methanol/ether , the compound had a melting point of 162-163°C (with decomposition).
Example 2 3-(1«2 , ,4— etrahydroisoquinolinyl)-sydnonimine 9.2 g (0.05 mol) of N-amino-l,2, 3, -tetrahydro-isoquinoline hydrochloride and 75 ml of water were cooled to 5°C in an ice hath, A solution of 3.5 g (0.05 mol) potassium cyanide in 7.0 ml water was then added to this mixture in the course of 15 minutes,. I the course of a further 15 minutes, 3.8 ml of a 40% formaldehyde solution (0.05 mol) were added while stirring, the mixture stirred for one hour, brought to room temperature and stirred for another hour. The mixture was then again cooled to 5°C and sufficient N hydrochloric acid added to obtain a pH of 2. 3.83 g (0, 05 mol) sodium nitrite in 7. ml water were added, and the pH of the solution was kept low by gradual addition of about 20 ml 2N hydrochloric acid.
The nitroso-derivative thus obtained was extracted with chloroform yielding 11 g of crude product. The latter was slowly introduced while stirring and cooling into 120 ml methanolic hydrochloric acid, the resulting solution was evaporated in vacuo at 30°C, and the residue chromatographed on silica. Elution was effected with chloroform containing 10% methanol. There methanol/ether , melted at 155°C (with decomposition).
Example 3 1 1 3-(4- -Methyl-piperazinyl-1 )-sydnonimine To a mixture consisting of 10 g (0.066 mol) 1-amino- -methylpiperazine-hydrochloride and 30 ml water, cooled to 5°C in an ice "bath, a solution of 4-.4- g potassium cyanide (0.066 mol) in 25 ml of water was added while stirring. In the course of 30 minutes while 5 ml of a 4-0% formaldehyde solution (0.066 mol) were then introduced at the same temperature, the mixture stirred for one hour, the solution brought to room temperature and stirred for another hour. The mixture was then again cooled to 5°C» and 3.5 ml concentrated hydrochloric acid and subsequently 4.6 g (0.066 mol) sodium nitrite dissolved in 75 ml water were added dropwise. The pH-value of the solution was kept low by the gradual addition of 3.5 ml concentrated hydrochloric acid.
The nitroso-compound was extracted with chloroform and the 13.8 g crude product obtained were introduced slowly while cooling into 70 ml methanolic hydrochloric acid. The resulting 3-(4- -methyl-piperazinyl-1 )-sydnonimine hydrochloride crystallized spontaneously from the solution. The crystal-containing solution was evaporated to dryness and recrystallized from ethanol.
There were obtained in this manner 9.9 g. (59% of theory) of end-product, melting at 187 - 188°C (with decomposition) Example 4- 3-Hexamethylene-imino-sydnonimine then cooled to 5°C in an ice hath and a solution of 66 g (1 mol) potassium cyanide in 150 ml water added over 30 minutes. In. the course of a further JO" minutes-, 75 ml of a 40% formaldehyde solution (1 mol) were added, the mixture stirred for one hour and brought to room temperature in the course of another hour. After renewed cooling to 5°C, 5 ml concentrated hydrochloric acid and subsequently 69 g (1 mol) sodium nitrite in 140 ml water were slowly added. The pH of the solution was maintained in the acid range by gradual addition of 45 ml concentrated hydrochloric acid.
The nitroso-derivative was extracted with chloroform and the resulting, 172 g crude product were introduced slowly while stirring into one litre methanolic hydrochloric acid. The resulting solution was concentrated in vacuo at 30°0 and chromatographed on silica. After elution with chloroform containing 10% methanol, 113.8 g (52% of theory) of 3-hexamethylene-imino-sydnonimine hydrochloride were obtained, which, after recrystalliza-tion from methanol/ether had a melting point of 153 -154°C (decomposition).
Example 5 3-Diallylamino-sydnonimine To 72 g (0.64 mol) 1,1-diallylhydrazine suspended in 150 ml water, there were added slowly at 10°C while stirring, 45 ml pf concentrated hydrochloric acid. The mixture was cooled to 5°C in an ice bath and a solution of 3 g (0.64 mol) potassium cyanide in 90 ml water added in the course of 0 minutes. The tem erature was maintained again cooled to 5°C, and 50 ml of 4—N hydrochloric acid added in the course of 50 minutes. A solution of 4-8 g sodium nitrite in 100 ml water (0.07 mol) was then added and the pH-value was kept low by the gradual addition of 1 0 ml of 4-N hydrochloric acid. The mixture was stirred for one hour at a temperature of 5 - 10°C, brought to room temperature and extracted three times with ohloro-form. The chloroform extracts were dried over sodium sulphate, filtered and brought to dryness in vacuo. 122 g of crude product were obtained, which were dissolved in 180 ml of methanol and added slowly to 2 litres methanolic hydrochloric acid. The resulting solution was concentrated in vacuo at 50°C and chromatographed on silica. After elution with chloroform containing 10% methanol, there were obtained 78 g (56% of theory) of 3-diallylamino-sydnonimine hydrochloride, which, after recrystallization from methanol/ether had an Hp. of 94— 96°C (decomposition).
Example 6 3-Methyl-benzylamino-sydnonimine 60 ml of concentrated hydrochloric acid were added with stirring and cooling to a mixture of 87 g (0.64-mol) 1-benzyl-l-methylhydrazine suspended in 200 ml water. The mixture was cooled to 5°C in an ice bath and a solution of 42 g (0.64 mol) potassium cyanide in 90 ml water added in the course of 30 minutes. Within a further 0 minutes, at the same temperature, 50 ml (0.64- mol) of a 4-0% formaldehyde solution were added, Example 18 -Diallylamino-4-phenylethyl-sydnonimine To 56.3 g (0.05 mol)l,l-diallyl-hydrazine there were added with cooling 150 ml water and 20 ml concentrated hydrochloric acid. The mixture was cooled to 5°C in an ice bath and a solution of 52. 5 g (0.5 mol) potassium cyanide in 100 ml water was added thereto in the course of 30 minutes, followed "by the addition, in the course of another hour, of 67.1 g ( 0.5 mol) phenylpropionaldehyde . The mixture was then stirred for one hour, brought to room temperature and stirred for another hour. It was then again cooled to 5°C> and 24 ml concentrated hydrochloric acid added and then 3 , 5 g (0. 5 mol) sodium nitrite in 100 ml water.
The nitroso-derivative thus formed was extracted with chloroform, to yield 136 g of crude product, which was added slowly dropwise to 1 , 5 litres methanolic hydrochloric acid while stirring and cooling. The resulting solution was concentrated in vacuo at 30°C and the residue chromatographed on silica. 115g (74·% of the theory) of 3-diallylamino-4-phenylethyl-sydnonimine hydrochloride were obtained which, after recrystallization from isopropanol/ether, had a melting temperature of 113-114°C (decomposition).
The following further compounds were obtained by the method described in Example 18: Yield " '· Example n _ _ _ _ ,, _ A (% xP« No. G o m.p-o u n d theory) °G 19 3-diallylamino- -methyl- 71 HO - 112 d com Example 21 g 3-Piperidino-H -acetyl-sydnonimine To a mixture of 25 ml acetic anhydride and 5 ml pyridine 2„ 5 S (0.0125 mol) 5-piperidino-sydnonimine hydrochloride were added. The mixture was heated to 30°C until complete dissolution, and was then left to stand for 3 hours, at room temperature and then for two days at 5°C. The crystals which have separated by the end of this period were filtered off. The mother liquor was evaporated to dryness and the remaining resinous substance was crystallized'from methanol/ether. The two crystalline fractions obtained were identical and constituted a yield of 1.96 g ( 33%, calculated on the amount of hydrazine hydrochloride employed) of 3-piperidino-N^-acetyl-sydnonimine, melting at 175°C (decomposition).
Example 22 3-Dimethylamino-N 6-ethoxycarbonyl-sydnonimine hydrochloride A mixture consisting of 16.5 g (0.1 mol) of 3-dimethyl-amino-sydnonimine hydrochloride and 200 ml pyridine was cooled to -10°C and was admixed with 16.5 g (0.10 mol) of ethyl chloroformate added drop-wise. The temperature was then allowed to rise firstly to 5°C and then to room temperature, and the mixture was stirred at this temperature for 3 hours. 500 ml of water were then added and the solution was extracted with chloroform. The chloroform-extracts a o to and the crystals then separating were filtered off.
There were obtained in this manner 16 g (34%) of 3-dimethy1amino-N^-ethoxycarbony1-sydnonimine hydro-chloride, melting at 155°C (decomposition).
Example 23 g 3-Dimethylamino-N -3-nitrofuroyl-sydnonimine 150 ml pyridine were admixed with 12 g (0.07 mol) 3-dimethylamino-sydnonimine hydrochloride and 17.5 g (0.1 mol) 5-nitrofuroyl chloride. The mixture was allowed to stand at room temperature for 3.5 hours, then overnight at 0°C, The excess of acid chloride was then destroyed by addin 25 ml water and the solution was distributed between 100 ml water and 200 ml chloroform. The two layers were then separated and the aqueous phase was extracted four times with 150 ml portions of chloroform. The combined chloroform solutions were dried and the solvent was removed in vacuo. The remaining resin was crystallised from acetonitrile/ether. There were obtained in this manner 12.2 g (43% of theory) of 3- 6 dimethylamino-N -5-nitrofuroyl-sydnonimine , with an Mp, of 218 - 219°C (decomposition), after recrystallization from acetonitrile-ether.
The following further compounds were obtained by the process according to the invention: Example Yield No. C o m p o u n d theory) 24 3-diallylamino-N6-acetyl- 36 108 - 109 sydnonimine hydrochloride (decomp.) 3-hexamethyleneimino-N6-benzoyl- 32 149 - 150 s dnonimine h drochloride decom Yisld Example No. C o m p o u n d theory) 27 3-dimethylamino-N -phenylpro- 35 153 - 154 pionyl-sydnonimine (decomp. ) hydrochloride 28 3-piperidino-N -ethoxycarbonyl- 3 139 - 141 sydnonimine hydrochloride (decomp. ) 29 3-diallylamino-4-ethyl-N6- 7 95 - 96 ethoxy-carbonyl-sydnonimine (decomp. ) hydrochloride 6 3-dimethylamino-rN -acetyl- 54 174 sydnonimine hydrochloride (decomp. ) g 31 3-plperidino-N -acetyl-sydnoni- 31 96 - 97 mine methiodide (decomp. ) 32 3-(1-acetylhomopiperazino)-N^- 31 179 ' acetyl-sydnonimine - hydrochloride (decomp. ) ✓ 33 6 3-?dimethylamino-N -benzoyl- 60 178 sydnonimine hydrochloride (decomp. ) 6 34- 3-dimethylamino-N -o-chloro- 67 16 - 168 benzpyl-sydnonimine hydrochloride (decomp. ) g .
Ks 35 3-dimethylamino-N -p-chloroben- 62 184 - 185 zoyl-sydnonimine hydrochloride (decomp. ) 3-dimethylamino-N^-o-methylben- 63 160 - 162 zoyl-sydnonimine hydrochloride (decomp. ) ^37 3-dimethylamino-N -cyclohexyl- 59 187 carbonyl-sydnonimine (decomp. ) hydrochloride .g 638 3-dimethylamino-N -cyclopropyl- 48 181 - 184 carbonyl-sydnonimine (decomp. ) hydrochloride g L/39 3-dimethylamino-N -nicotinoyl- 57 198 - 199 sydnonimine hydrochloride (decomp. ) ^ 0 3-dimethylamino-N -tert . -butyl- 49 168 acetyl-sydnonimine (decomp. ) hydrochloride - g 1 3-morpholino-N -cyclohexylcarbo- 61 187 nyl-sydnonimine hydrochloride (decomp. ) Example 42 Dragees (a) 3-(l,2,3,4-Tetrahydro-isoquinolinyl)- 50 mg sydnonimine hydrochloride Lactose 65 m Maize starch 90 mg Secondary calcium phosphate 35 m Soluble starch 3 mg Magnesium stearate 3 mg Colloidal silica 4 mg 250 mg (b ) 3-Dimethylamino-sydnonimine hydrochloride . ·■ · 30 mg Lactose 55 mg Maize starch - 75 mg Secondary calcium phosphate 30 mg Soluble starch 3 mg Magnesium stearate 3 mg Colloidal silica 4 mg 200 mg Example 43 Tablets 3-N-methyl-piperazino-sydnonimine ;35 m hydrochloride Lactose 60 mg Maize starch 35 mg Soluble starch 4 mg Magnesium stearate 1 mg 135 mg Example 44 Drops (20.0 mg in 1 ml - 20 drops) 3-Hexamethyleneimino-sydnonimine 2.00 g hydrochloride Methyl-p-hydrqxy-benzoate 0.07 S Ethyl-p-hydroxy-benzoate 0.03 g Ethanol, 96% 20 ml Demineralised water q.s.p. 100 ml Example $ Ampoules 6 3-piperidino-N -acetyl- 20.0 mg sydnonimine hydrochloride •Sodium chloride 18.0 mg Distilled water q.s.p. 2 ml Example 46 Capsules The contents of each capsule are composed of:: 3-dimethylamino-N -(5-nitrofuroyl)- sydnonimine 25 mg Maize starch 175 mg

Claims (2)

1.
2. 3-Dimethylamino-N -(5-nitrofuroyl)-sy
IL6728432A 1966-08-09 1967-08-01 Substituted 3-amino-sydnonimines and processes for their manufacture IL28432A (en)

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JP (1) JPS537433B1 (en)
BE (1) BE702448A (en)
BG (1) BG15571A3 (en)
CA (1) CA925083A (en)
CH (1) CH507277A (en)
DE (1) DE1670127A1 (en)
DK (1) DK126594B (en)
ES (1) ES343818A1 (en)
FI (1) FI49420C (en)
FR (2) FR1551013A (en)
GB (1) GB1198283A (en)
IL (1) IL28432A (en)
NL (1) NL153195B (en)
PH (1) PH10178A (en)
SE (1) SE343304B (en)
YU (1) YU34691B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2930736A1 (en) * 1979-07-28 1981-02-12 Cassella Ag PHARMACOLOGICALLY ACTIVE, SUBSTITUTED 3-AMINO-SYDNONIMINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE
DE3837327A1 (en) * 1988-11-03 1990-05-10 Cassella Ag SUBSTITUTED 3-AMINO-DYNONOMINES, PROCESS FOR THEIR PREPARATION AND THEIR USE
DE3921460A1 (en) * 1989-06-30 1991-01-03 Cassella Ag SUBSTITUTED 3-AMINO-DYNONOMINES, PROCESS FOR THEIR PREPARATION AND THEIR USE
DE3921796A1 (en) * 1989-07-03 1991-01-17 Cassella Ag SUBSTITUTED 3-AMINO-DYNONOMINES, PROCESS FOR THEIR PREPARATION AND THEIR USE
DE4025604A1 (en) * 1990-08-13 1992-02-20 Cassella Ag 3-DICYCLOHEXYLAMINO-SYDNONIMINE, METHOD FOR THE PRODUCTION AND USE THEREOF
DE4028679A1 (en) * 1990-09-10 1992-03-19 Cassella Ag SUBSTITUTED 3-AMINOSYDNONIMINE, METHOD FOR THE PRODUCTION AND USE THEREOF
WO1993018767A1 (en) * 1992-03-24 1993-09-30 Cassella Aktiengesellschaft Use of sydnonimines to treat erectile dysfunction
DE4337335A1 (en) * 1993-11-02 1995-05-04 Cassella Ag Process for the preparation of Sydnoniminium hydrogen sulfate

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GB1198283A (en) 1970-07-08
FI49420C (en) 1975-06-10
CA925083A (en) 1973-04-24
NL153195B (en) 1977-05-16
CH507277A (en) 1971-05-15
FR8428M (en) 1971-07-08
ES343818A1 (en) 1968-12-01
NL6710945A (en) 1968-02-12
PH10178A (en) 1976-09-16
FR1551013A (en) 1968-12-27
BE702448A (en) 1968-02-08
YU156567A (en) 1979-07-10
JPS537433B1 (en) 1978-03-17
SE343304B (en) 1972-03-06
DK126594B (en) 1973-07-30
DE1670127A1 (en) 1970-12-03
FI49420B (en) 1975-02-28
BG15571A3 (en) 1976-06-21
YU34691B (en) 1979-12-31

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