CH533105A - Pyrrolidine derivs hypotensive - Google Patents
Pyrrolidine derivs hypotensiveInfo
- Publication number
- CH533105A CH533105A CH499471A CH499471A CH533105A CH 533105 A CH533105 A CH 533105A CH 499471 A CH499471 A CH 499471A CH 499471 A CH499471 A CH 499471A CH 533105 A CH533105 A CH 533105A
- Authority
- CH
- Switzerland
- Prior art keywords
- evapd
- etoh
- alkyl
- formula
- hrs
- Prior art date
Links
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title abstract 8
- 208000001953 Hypotension Diseases 0.000 title abstract 2
- 208000021822 hypotensive Diseases 0.000 title abstract 2
- 230000001077 hypotensive effect Effects 0.000 title abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- KTDKAQFODMVOLP-UHFFFAOYSA-N 2-pyrrolidin-1-ylguanidine Chemical class NC(=N)NN1CCCC1 KTDKAQFODMVOLP-UHFFFAOYSA-N 0.000 claims description 4
- GAZRNXIMWKZADY-UHFFFAOYSA-N 3,5-dimethylpyrazole-1-carboximidamide Chemical compound CC=1C=C(C)N(C(N)=N)N=1 GAZRNXIMWKZADY-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical class NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 claims description 2
- SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical compound NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract description 5
- 239000003054 catalyst Substances 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 229910052703 rhodium Inorganic materials 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- BZZXQZOBAUXLHZ-UHFFFAOYSA-N (c-methylsulfanylcarbonimidoyl)azanium;sulfate Chemical compound CSC(N)=N.CSC(N)=N.OS(O)(=O)=O BZZXQZOBAUXLHZ-UHFFFAOYSA-N 0.000 abstract 1
- PIBIHODWSMJTFG-UHFFFAOYSA-N 1-chloro-2-methylbut-3-yn-2-ol Chemical compound ClCC(O)(C)C#C PIBIHODWSMJTFG-UHFFFAOYSA-N 0.000 abstract 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 abstract 1
- 229910052593 corundum Inorganic materials 0.000 abstract 1
- XZUAPPXGIFNDRA-UHFFFAOYSA-N ethane-1,2-diamine;hydrate Chemical compound O.NCCN XZUAPPXGIFNDRA-UHFFFAOYSA-N 0.000 abstract 1
- 230000003287 optical effect Effects 0.000 abstract 1
- 235000011149 sulphuric acid Nutrition 0.000 abstract 1
- 229910001845 yogo sapphire Inorganic materials 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- -1 pyrrole alkylamines Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BCUPGIHTCQJCSI-UHFFFAOYSA-N chloromethanol Chemical compound OCCl BCUPGIHTCQJCSI-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000012609 strong anion exchange resin Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/04—Compounds containing oxirane rings containing only hydrogen and carbon atoms in addition to the ring oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
(A) Method for cmpds. (I):- - and salts of (I), including all optical and geometrical stereoisomers. - (B) The cpds. (II) and some (III) - where R, R1 and R3 = H or (1-6C) alkyl - R2 = (1-6C) alkyl or cycloalkyl - R4 and R5 = H or (1-6C) alkyl, one of them may be NH2 or NO2 or - R4 + R5 together may be -CH2CH2- - n = 2-8 - Hypotensives with low side effects. - (a) 3-Chloromethylbut-1-yne-3-ol (11.85 g.), ethylenediamine hydrate (63.4 ml.), and EtOH (40 ml.), were refluxed 17 hrs., evapd. in vac., 40% NaOH (10 ml.) added, H2O removed by azeotropic distn. with PhH, evapd., and distilled, giving the pyrrol (III) (5.82 g.), b.p. 65.5-66 deg./2 mm. - (b) This (12.4 g.) was hydrog. at 25 deg. and 35 kg/cm2 in EtOH (250 ml.) and 5N-HCl (40 ml.), over a 5% Rh.-Al2O3 catalyst (5.0 g.), for 60 hrs. The mixture was filtered, evapd., basified (d.NaOH), extd. with Et2O, and distilled, giving the pyrrolidine (II) (8.72 g.), b.p. 66 deg./14 mm. - (c) This (3.84 g.), S-methylisothiouronium sulphate (4.17 g.), EtOH (40 ml.), and H2O (20 ml.), were refluxed 3.5 hrs., cooled, filtered, neutralised with 5N H2SO4 (6.0 ml.), evapd. in vac., and the residue refluxed with EtOH, giving (I) (7.31 g., 91%), m.p. 233-7 deg. (dec.).
Description
Verfahren zur Herstellung von Pyrrolidinoguanidin-Verbindungen Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung neuer Pyrrolidino-Guanidin-Verbindungen. Es handelt sich dabei um Substanzen, welche gute blut drucksenkende Eigenschaften mit geringen Nebenwir kungen aufweisen.
Bei den neuen Verbindungen handelt es sich um solche der Formel (I), sowie um deren ungiftige Säure additionssalze:
EMI0001.0001
(HI) In der Formel bedeuten R, R1 und R,3 Wasserstoff oder niederes Alkyl. R2 ist niederes Alkyl oder Cyclo- alkyl.
n ist eine ganze Zahl von 2 bis B.
Die neuen Verbindungen können. als Cis- und Trans isomere vorkommen, wobei beide dieser Formel nach dem erfindungsgemässen Verfahren herstellbar sind. Da die Verbindungen ebenfalls asymmetrische Kohlenstoff atome enthalten können sie auch in optisch aktiven existieren, welche wiederum gleichfalls sich nach dem erfindungsgemässen Verfahren herstellen lassen. Der im vorstehenden benutzte Ausdruck niederes Alkyl gilt für Alkylgruppen mit 1 bis 6 Kohlenstoffato men.
Das erfindungsgemässe Verfahren zur Herstellung der Verbindungen der Formel (1) ist dadurch gekenn zeichnet, dass man ein Pyrrolidinoamin der Formel (II):
EMI0001.0009
oder ein Salz davon mit einem gegebenenfalls alkylierten 1-Guanylpyrazol, insbesondere mit 1-Guanyl-3,5-dime- thylpyrazol, oder mit einem Salz davon umsetzt.
Vorzugsweise wird das guanylierende Agens mit dem Amin oder dessen Salz in einem inerten Lösungsmittel erwähnt, wobei die Verbindung der Formel (I) entsteht.
Die als Ausgangsprodukt verwendeten Pyrrolidino- alkylamine können durch katalytische Hydrierung in Lösung eines entsprechenden Fyrrols der Formel hergestellt werden:
EMI0001.0015
Hierbei kann man als Katalysator z.B. Rhodium auf Aluminiumoxyd bzw. einen 5 oder 10% Palladium auf Kohle enthaltenden Katalysator verwenden. Falls R oder R1 andere Reste sind als ein Wasserstoffatom lassen sich durch diese Reaktion Gemische von Cis-trans-Isomeren herstellen.
Zar Herstellung der Pyrrolalkylamine der Formel (III) können verschiedene Verfahren zur Anwendung ge langen und insbesondere: (1) Umsetzung eines acetyleni- schen Chlorcarbinols ClCHR - CR2(OH) - C-CR1 oder ClCHR - CR2(OH) - CH2 - C=CH mit einem Amin NH2 - (CH2)n - NH2.
(2) Umsetzung eines acetylenischen Eiloxids der For meln
EMI0001.0019
oder
EMI0002.0000
mit einem Amin NH2-(CH2)n-NH2.
(3) Überführung eines Pyrralalkanols der Formel
EMI0002.0001
a in ein reaktives Derivat der Formel
EMI0002.0002
, worin in der letzteren Formel X ein Halogenatom oder der Rest einer Sulfonsäure insbesondere p-Toluolsulfon- säure ist und Umsetzung dieser Verbindung mit einem Amin R3NH2.
Die Pyrrolidinoalkylamine der Formel (II) sind gleichfalls neue Verbindungen, wie dies auch für eine Anzahl der anderen im vorliegenden beschriebenen Zwi schenprodukte zutrifft.
Die neuen Pyrrolidinoguanidine der Formel (I) las sen sich in pharmazeutische Kompositionen einarbeiten mit geeigneten pharmazeutischen Trägern. Geeignete Trägerstoffe sind z.B. Excipientien, Füllstoffe, Binde mittel und steriles Waser, woraus sich Zubereitungen zur oralen parenteralen oder anderswie gearteten Ver abreichung herstellen lassen.
<I>Beispiel</I> Eine Mischung von 1-Guanyl-3,5-dimethylpyrazol- nitrat u. 1-(α-Aminoäthyl)-2,4-dimethylpyrrolidin, wur den 2¸ Stunden lang unter Rühren erwärmt. Der Über- schuss an Amin wurde im Vakuum abgetrieben und der Rückstand in Wasser gelöst. Es erfolgte Überführung in das 1-(α-Guanidinoäthyl)-2,4-dimethylpyrrolidinsulfat- hydrat durch Behandlung mit einem starken Anionen austauscherharz in Form des Sulfates. Die erhaltene Lö sung wurde unter vermindertem Druck eingedampft und der Rückstand aus wässrigem Äthanol kristallisiert. Das erhaltene Produkt wurde aus Aceton/Wasser umkristal lisiert.
Smp. = 291 bis 292 C (Zers.). Es handelte sich um 1-(α-Guanidinoäthyl)-2,4-dimethylpyrrolidin-sulfat- -hydrat.
Process for the preparation of pyrrolidino-guanidine compounds The present invention relates to a process for the preparation of new pyrrolidino-guanidine compounds. These are substances that have good blood pressure-lowering properties with few side effects.
The new compounds are those of the formula (I) and their non-toxic acid addition salts:
EMI0001.0001
(HI) In the formula, R, R1 and R, 3 denote hydrogen or lower alkyl. R2 is lower alkyl or cycloalkyl.
n is an integer from 2 to B.
The new connections can. occur as cis and trans isomers, both of these formulas being producible by the process according to the invention. Since the compounds also contain asymmetric carbon atoms, they can also exist in optically active ones, which in turn can also be produced by the process according to the invention. The term lower alkyl used in the above applies to alkyl groups having 1 to 6 carbon atoms.
The process according to the invention for the preparation of the compounds of the formula (1) is characterized in that a pyrrolidinoamine of the formula (II):
EMI0001.0009
or a salt thereof is reacted with an optionally alkylated 1-guanylpyrazole, in particular with 1-guanyl-3,5-dimethylpyrazole, or with a salt thereof.
Preferably the guanylating agent is mentioned with the amine or its salt in an inert solvent, whereby the compound of formula (I) is formed.
The pyrrolidinoalkylamines used as the starting material can be prepared by catalytic hydrogenation in a solution of a corresponding fyrrole of the formula:
EMI0001.0015
The catalyst here can be e.g. Use rhodium on aluminum oxide or a catalyst containing 5 or 10% palladium on carbon. If R or R1 are radicals other than a hydrogen atom, mixtures of cis-trans isomers can be produced by this reaction.
To prepare the pyrrole alkylamines of the formula (III), various processes can be used, and in particular: (1) Reaction of an acetylenic chlorocarbinol ClCHR - CR2 (OH) - C-CR1 or ClCHR - CR2 (OH) - CH2 - C = CH with an amine NH2 - (CH2) n - NH2.
(2) Implementation of an acetylenic oxide of the formula
EMI0001.0019
or
EMI0002.0000
with an amine NH2- (CH2) n-NH2.
(3) Conversion of a pyrralalkanol of the formula
EMI0002.0001
a into a reactive derivative of the formula
EMI0002.0002
in which in the latter formula X is a halogen atom or the residue of a sulfonic acid, in particular p-toluenesulfonic acid, and reaction of this compound with an amine R3NH2.
The pyrrolidinoalkylamines of the formula (II) are also new compounds, as is also the case for a number of the other intermediate products described herein.
The new pyrrolidinoguanidines of the formula (I) can be incorporated into pharmaceutical compositions with suitable pharmaceutical carriers. Suitable carriers are e.g. Excipients, fillers, binders and sterile water, from which preparations for oral parenteral administration or other types of administration can be produced.
<I> Example </I> A mixture of 1-guanyl-3,5-dimethylpyrazole nitrate u. 1 - (α-Aminoethyl) -2,4-dimethylpyrrolidine, was heated with stirring for 2¸ hours. The excess of amine was driven off in vacuo and the residue was dissolved in water. It was converted into 1 - (α-guanidinoethyl) -2,4-dimethylpyrrolidine sulfate hydrate by treatment with a strong anion exchange resin in the form of the sulfate. The solution obtained was evaporated under reduced pressure and the residue was crystallized from aqueous ethanol. The product obtained was recrystallized from acetone / water.
M.p. = 291-292 C (dec). It was 1 - (α-guanidinoethyl) -2,4-dimethylpyrrolidine sulfate hydrate.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB55708/67A GB1185080A (en) | 1967-12-07 | 1967-12-07 | Pyrrolidines |
| CH1833468A CH534679A (en) | 1967-12-07 | 1968-12-09 | Process for the preparation of pyrrolidino compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH533105A true CH533105A (en) | 1973-01-31 |
Family
ID=25720857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH499471A CH533105A (en) | 1967-12-07 | 1968-12-09 | Pyrrolidine derivs hypotensive |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH533105A (en) |
-
1968
- 1968-12-09 CH CH499471A patent/CH533105A/en not_active IP Right Cessation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE965036C (en) | Process for the preparation of p-(bis-2-chloroethylamino)-ª‰-phenyl-alanine | |
| DE2527914C3 (en) | Vincamine derivatives, processes for their preparation and pharmaceutical agents | |
| DE2929517A1 (en) | PINE DERIVATIVES, METHOD FOR THEIR PRODUCTION AND PHARMACEUTICAL PREPARATIONS CONTAINING THE SAME | |
| DE69102762T2 (en) | BETA-PHENYLISOSER DERIVATIVES, THEIR PRODUCTION AND THEIR USE. | |
| CH533105A (en) | Pyrrolidine derivs hypotensive | |
| DE2454950C2 (en) | Process for the preparation of 2-aminobutan-1-ol and its acid addition salts | |
| DE2303176A1 (en) | SUBSTITUTED 5-CHROMANOLS, METHOD FOR THEIR MANUFACTURING AND MEDICINAL PREPARATIONS CONTAINING THESE COMPOUNDS | |
| DE69014434T2 (en) | Crystalline aluminophosphates and related compounds. | |
| DE1693032B1 (en) | Process for the preparation of 1,2-disubstituted adamantane compounds | |
| DE2718533C3 (en) | Catalyst system and its use for asymmetric hydrogenation | |
| AT208872B (en) | Process for the preparation of new 1,4-diazacycloheptanes | |
| AT317209B (en) | Process for the preparation of new phenylimidazolidinone derivatives and their salts | |
| DE948687C (en) | Process for the production of dialkylxanthine capsules | |
| AT334874B (en) | PROCESS FOR THE PREPARATION OF NEW 2,2,3-TRIMETHYL-7-AMINONORBORNANES AND THEIR ACID ADDITION SALTS | |
| DE1199753B (en) | Process for the preparation of glucuronic acid amides and their N-alkyl substitution products | |
| DE842345C (en) | Process for the preparation of heterocyclic nitrogen compounds | |
| DE2511576A1 (en) | METFORMIN-CLOFIBRATE, THE METHOD FOR MANUFACTURING IT AND THE MEDICINAL PRODUCT CONTAINING IT | |
| DE1811832A1 (en) | Pyrrolidine derivs hypotensive | |
| DE2628042B2 (en) | 3-Amino-tricyclo [53.1.0.3A1 -undecane, its acid addition salts and process for the preparation of these compounds | |
| AT266080B (en) | Process for the preparation of the new 1-isopropylamino-2-hydroxy-3- (o-lower alkoxymethyl-phenoxy) -propanes and their salts | |
| DE859892C (en) | Process for the preparation of substituted piperidinoacetic acid esters | |
| AT282594B (en) | PROCESS FOR THE PREPARATION OF NEW RACEMIC OR OPTICALLY ACTIVE (1-2'-NITRILOPHENOXY) -2-HYDROXY-3-ISOPROPYLAMINOPROPANE AND ITS SALTS | |
| DE2263093A1 (en) | 7-METHOXY-2,3-DIHYDROBENZOFURA DERIVATIVES AND THE PROCESS FOR THEIR PRODUCTION | |
| DE2027433C3 (en) | Basic ß-thienyl derivatives, processes for their preparation and pharmaceuticals containing them | |
| AT309395B (en) | Process for the preparation of (+) - 2,2 '- (ethylenediimino) -di-1-butanol-dihydrochloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |