GB1595031A - 3-isobutoxy-2-pyrrolidino-n-phenyl-n-benzyl propylamine and its salts - Google Patents

3-isobutoxy-2-pyrrolidino-n-phenyl-n-benzyl propylamine and its salts Download PDF

Info

Publication number
GB1595031A
GB1595031A GB1506/78A GB150678A GB1595031A GB 1595031 A GB1595031 A GB 1595031A GB 1506/78 A GB1506/78 A GB 1506/78A GB 150678 A GB150678 A GB 150678A GB 1595031 A GB1595031 A GB 1595031A
Authority
GB
United Kingdom
Prior art keywords
compound
product
pyrrolidino
isobutoxy
formula
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.)
Expired
Application number
GB1506/78A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre Europeen de Recherches Mauvernay CERM
Original Assignee
Centre Europeen de Recherches Mauvernay CERM
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
Application filed by Centre Europeen de Recherches Mauvernay CERM filed Critical Centre Europeen de Recherches Mauvernay CERM
Publication of GB1595031A publication Critical patent/GB1595031A/en
Expired legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Cardiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The compound of formula (I) has a molecular mass M of 366 and a boiling point B.p.0.5 of 192 DEG C. It can be used for the treatment of cardiovascular ailments, especially for the treatment of angor (angina). <IMAGE>

Description

(54) 3-ISOB UTOXY-2-PYRROLIDINO-N-PHENYL- N-BENZYL PROPYLAMINE AND ITS SALTS (71) We, CENTRE EUROPEEN DE RECHERCHES MAUVERNAY, a French Body Corporate, of 63203 Riom Cedex, France, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to an N-phenyl N-benzyl propylamine and to a process for obtaining the same, as well as to pharmaceutical compositions containing the same.
The compound according to this invention is 3 - isobutoxy - 2 - pyrrolidino N - phenyl - N - benzyl propylamine, having the following formula:
The physico-chemical characteristics of the compound of formula (I) are given hereinafter.
This compound is useful as a medicament, and notably as the active principle in the treatment of cardiovascular disorders and particularly in the treatment of angina pectoris, also named stenocardia.
Compounds are already known, which correspond to the general formula:
wherein A is an amino group, and Ar and Ar' are each an aromatic group. But these compounds which, among those known to one with ordinary skill in the art, most closely resemble the compound of the invention, are described as having antihistaminic properties (Erhart Ruschig Arzneimittel I, pages 208-210).
The invention also relates to a process for obtaining the compound of formula I, starting from a 2,3-dibromopropionic acid ester.
The 2,3-dibromopropionic acid esters, and notably the ethyl ester of 2,3dibromopropionic acid, are known compounds which can be prepared by processes known to those with ordinary skill in the art.
In a first step, a 2,3-dibromopropionic ester is treated with isobutanol in the presence of sodium.
In a second step, the product of step I is treated with an excess of pyrrolidine.
In a third step, the 3 - isobutoxy - 2 - pyrrolidinopropionic acid ester obtained in step 2 is treated with N-benzyl-aniline magnesium bromide.
In a fourth step, the amide function of the product of step 3 is reduced, preferably with LiAIH4 in ether, thus obtaining 3 - isobutoxy - 2 - pyrrolidino N - phenyl - N - benzyl - propylamine.
If desired, the monohydrate of the monohydrochloride of this last compound can be obtained by treatment with dilute aqueous hydrochloric acid.
The addition salts of the compound of formula I with pharmaceutically acceptable organic or inorganic acids also lie within the scope of the invention.
As an example, the synthesis of the compound of the present invention is described hereinbelow.
l.t step:
CH3 C3\ Br- cH-cH-cO,e rHg Na Lr C3\ Br cH 1 CH3 2nd step: cH H"3 /cn oicaWS o - crb4-oica C113 to1umt C3 \CH-CII1-O-CH2-CH-CoZC2H5 c3 < > 3rd step: 4th step
Reduction of the amide function of compound II with LiAIH4 in ether to give the compound of formula I.
Each of these steps will now be described in greater detail.
Ist step 5.1 g of sodium in pieces was introduced into 150 ml of isobutanol. Stirring was effected, with heating if necessary, until the sodium had dissolved.
The product was cooled to -50C and 0.2 mole (52 g) of the ethyl ester of dibromopropionic acid
was added dropwise at this temperature.
Stirring was effected for 2 to 3 hours at ambient temperature.
The NaBr salt which formed during the reaction was filtered off. The isobutanol was evaporated. 200 ml of chloroform was added to the residue and the product was then washed with water.
The organic phase was dried over sodium sulfate and concentrated under reduced pressure.
After distillation, there was obtained 32 g of a product having a molecular weight M=253, a boiling point at 15 mm of mercury E,5=120 C, and the formula:
2nd step A triple excess of pyrrolidine was added to the product of step 1 in solution in toluene at 250C.
The product was heated for 2 to 3 hours.
The toluene was evaporated under reduced pressure; chloroform was added to the residue; the organic phase was washed with water, dried over sodium sulfate and evaporated.
After distillation of the crude product, an amino ester having the following formula was obtained:
M=243 E15=130 C; nD23=1,4485.
3rd step 0.5 mole of ethyl bromide was added dropwise to 0.15 gram atom of magnesium in 10 ml of anhydrous ether. After the magnesium had completely dissolved, 0.15 mole of N-benzyl aniline in 50 ml of diethyl ether was added dropwise. Reflux was maintained for 1 to 2 hours. 0.1 mole of the aminoester obtained in step 2 above was then added and the whole was maintained under reflux for 6 hours. After hydrolysis with 10 ml of NH4Cl-saturated water, the product was filtered and decanted. The precipitate was washed with diethyl ether and the ether phases were then combined and dried over sodium sulfate and concentrated under reduced pressure.
The dry extract was distilled and a compound having the following formula was obtained:
E05= 1 820C.
M=380.
4th step 0.025 mole of the amide obtained in step 3 was added to 0.05 mole of lithium aluminium hydride in 200 ml of anhydrous diethyl ether.
The reaction was maintained for 30 hours after heating under reflux.
After hydrolysis at OOC with a minimum of NH4Cl-saturated water, the product was filtered and the ethereal phase was decanted, dried over sodium sulfate and concentrated under reduced pressure. Distillation of the dry extract gave the product of formula I. (Eos=192 C).
Preparation of the Hydrochloride The basic product I was treated in water with dilute hydrochloric acid until it became acid.
The precipitate which formed was filtered, washed with water and dried.
The salt obtained was a monohydrate of the monohydrochloride with the empirical formula C24H34N2O, HCI, H2O. M=421.03.
Melting point 91+2 C.
Elementary analysis theoretical found C 68,46% 68,39% H 8,86% 8,82% N 6,65% 6,72% Cl 8,42% 8,36% Studies have shown that the compound of the invention had remarkable pharmacological properties in the field of cardiovascular disorders. This may be explained by the fact that, in addition to the properties common to coronarydilatation products, it has shown itself to possess ss-moderating or even p-inhibiting properties without, however, having undesirable /3-blocking effects, notably with respect to the lungs and myocardial contractility.
Owing to these properties, which are illustrated hereinafter by some pharmacological tests, the compound of the invention may be used therapeutically in the treatment of angina pectoris.
The accute LDso toxicity of the compound of the invention was tested on the mouse.
administration per os, LDso=1955 mg/kg (+200).
administered intravenously, LD50=23.5 mglkg (+1.3).
The compound of this invention, administered in a single dose (1.25 mg/kg intravenous) to anaesthetized dogs, whose thoraxes had been opened to position measuring apparatus, caused the following variations in hemodynamic parameters (average for 6 animals): Increase in coronary sinus flow: +49.7%+16%.
Increase in coronary sinus PVO2 +77.4%117.7%.
Slight increase in the amplitude of contractions of the right ventricule: +11.8%+2%.
Slowing down of heart rate -13 6V+2.6%.
Fall in systemic blood pressure: -20.1%#2.4% for a short time.
A more thorough study was conducted by carrying out experiments on dogs, consisting in stimulating p-adrenergic cardiovascular receptors by the administration of isoprenaline, and in opposing the tachycardiac, hypotensive and positive inotropic effects of this stimulation by the administration of the product of the invention by continuous perfusion (0.75 mg/kg/minute), using amiodarone as a control. The following table gives the percentages of inhibition observed when the total quantity administered had amounted to 16.875 mg/kg as determined by the Fisher-Student-t test:
percentage of inhibition compound 1 diastolic Positive administered \ Tachycardia hypotension inotropic effect compound of 76A15.9 60.9+8.7 38.5+7.4 the invention (significant (significant (significant at 1%) at 1%) at 1%) Amiodarone 73.1+4.7 16.2+6.1 23.2f 12.6 (significant (not (not at 1%) significant) significant) It will be seen that the product of this invention is more active than amiodarone in two out of the three parameters chosen.
Similarly, in the modified Bergamashi and Longoni test [Am. Heart. J., 86(3), 385-394 (1973)], concerning the initiation of an attack of angina pectoris by emotional stress in a subject suffering from coronary heart disease, the Robinson's sign [Charlier, Antianginal Drug, p. 29, Springer Verlag (1971)] was observed to be more favorable for the compound of this invention than for amiodarone.
As regards the lungs, the compound of this invention was observed to have no effect on histaminic bronchospasms in the guinea pig, whereas propanolol and practolol, both well known as p-blocking agents, potentialise this bronchospasm.
Example of Galenic Presentation and Dosage 100 mg tablets Compoundof this invention 100 mg Colloidal silica 8 mg Microcrystalline cellulose 85 mg Wheat starch 110 mg Polyvinylpyrrolidone (P.V.P.) 10 mg Methyl cellulose 9 mg Officinal talc 15 mg Magnesium stearate 3 mg 340 mg The compound of this invention was mixed with the first three excipients; these components were then moistened with a paste of PVP in 75% ethanol. The mixture was granulated and dried, the last three excipients then being added. After mixing, the powder obtained can be compressed to give tablets having an average weight of 340 mg.
Dosage 1 to 3 tablets comprising 100 mg of the product per day.
Generally speaking, the compound of this invention, associated with the usual excipients and/or vehicles, can be administered by the oral or intravenous routes at a daily dose of 100 to 300 mg.
In our prior patent specification No. B 1,377,327 we have described and claimed a process for the preparation of an n-propanolamine having the general formula:
in which A is a tertiary aliphatic, cycloaliphatic or heterocyclic amino group, R is a straight or branched chain alkyl group having 1--5 carbon atoms or an aralkyl group, Ar is an aromatic group and Ar' is an aromatic or heterocyclic group, which comprises heating an ether of a tertiary-aminopropylamine having the general formula: R-O-CH2-CHCl-CH2-A in which A and R as defined above, with an alkali metal derivative of an amine, which amine has the general formula Ar-CH2-NH-Ar1 in which Ar and Ar' are as above defined. The production of addition salts thereof is also claimed. No claim is made herein to the product obtained by the said process or addition salts thereof when Ar and Ar' are both phenyl, R is isobutyl and A is pyrrolidino.
Subject to the foregoing disclaimer, WHAT WE CLAIM IS: 1. 3 - Isobutoxy - 2 - pyrrolidino - N - phenyl - N - benzyl propylamine having the formula:
together with the addition salts thereof with pharmaceutically acceptable organic or inorganic acids.
2. A process for obtaining the compound claimed in Claim 1, which comprises: - - treating a 2,3-dibromo-propionic acid ester with isobutanol in the presence of sodium; ii -- treating the product of step i with an excess of pyrrolidine; iii -- reacting the 3-isobutoxy 2-pyrrolidino propionic acid ester obtained in step ii with N-benzyl aniline magnesium bromide; and iv - reducing the amide function of the product of step iii.
3. A process as claimed in Claim 2, wherein the product of step iv is further treated with dilute aqueous HCI to give the monohydrate of the monohydrochloride of the compound of formula I.
4. A pharmaceutical composition for treating cardiovascular disorders which comprises a compound as claimed in Claim I and a pharmaceutically acceptable excipient.
5. A composition as claimed in Claim 4, suitable for administration at a daily dose of 100 to 300 mg.
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (5)

**WARNING** start of CLMS field may overlap end of DESC **. Subject to the foregoing disclaimer, WHAT WE CLAIM IS:
1. 3 - Isobutoxy - 2 - pyrrolidino - N - phenyl - N - benzyl propylamine having the formula:
together with the addition salts thereof with pharmaceutically acceptable organic or inorganic acids.
2. A process for obtaining the compound claimed in Claim 1, which comprises: - - treating a 2,3-dibromo-propionic acid ester with isobutanol in the presence of sodium; ii -- treating the product of step i with an excess of pyrrolidine; iii -- reacting the 3-isobutoxy 2-pyrrolidino propionic acid ester obtained in step ii with N-benzyl aniline magnesium bromide; and iv - reducing the amide function of the product of step iii.
3. A process as claimed in Claim 2, wherein the product of step iv is further treated with dilute aqueous HCI to give the monohydrate of the monohydrochloride of the compound of formula I.
4. A pharmaceutical composition for treating cardiovascular disorders which comprises a compound as claimed in Claim I and a pharmaceutically acceptable excipient.
5. A composition as claimed in Claim 4, suitable for administration at a daily dose of 100 to 300 mg.
GB1506/78A 1977-01-25 1978-01-13 3-isobutoxy-2-pyrrolidino-n-phenyl-n-benzyl propylamine and its salts Expired GB1595031A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR7702058A FR2378024A1 (en) 1977-01-25 1977-01-25 NEW SUBSTITUTED PROPYLAMINE, OBTAINING AND APPLYING

Publications (1)

Publication Number Publication Date
GB1595031A true GB1595031A (en) 1981-08-05

Family

ID=9185890

Family Applications (1)

Application Number Title Priority Date Filing Date
GB1506/78A Expired GB1595031A (en) 1977-01-25 1978-01-13 3-isobutoxy-2-pyrrolidino-n-phenyl-n-benzyl propylamine and its salts

Country Status (12)

Country Link
JP (1) JPS5392764A (en)
AU (1) AU516479B2 (en)
BE (1) BE863214A (en)
CH (1) CH628889A5 (en)
DE (1) DE2802864C2 (en)
ES (1) ES466237A1 (en)
FR (1) FR2378024A1 (en)
GB (1) GB1595031A (en)
IL (1) IL53816A0 (en)
NL (1) NL189258C (en)
PT (1) PT67556B (en)
ZA (1) ZA78426B (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0096720A1 (en) * 1981-12-28 1983-12-28 Carter Wallace Process for the preparation of B-[(2-methylpropoxy)-methyl]-N-phenyl-N-(phenylmethyl)-1-pyrrolidineethanamine.
US4555514A (en) * 1984-01-18 1985-11-26 Riom Laboratoires C.E.R.M. "Rl-Cerm" S.A. 3-Alkoxy-2-(N-pyrolidino)-N-pyridyl-N-furyl(or thienyl) methyl-pyropyl amines useful as calcium antagonists
AU568694B2 (en) * 1983-11-11 1988-01-07 Akzo N.V. N-benzyl-n-phenyl-b-pyrrolidinyl-f-isobutoxy-propylamine
AU568704B2 (en) * 1983-11-11 1988-01-07 Akzo N.V. Ether of n-propanolamine derivative
AU569326B2 (en) * 1983-09-27 1988-01-28 Riom Laboratoires C.E.R.M. "Rl-Cerm" S.A. 2-(n-pyrrolidino)-3-isobutoxy-n-substituted phenyl-n-benzyl-propylamines
US4762834A (en) * 1984-01-18 1988-08-09 Riom Laboratoires C.E.R.M. "Rl-Cerm", S.A. 3-alkoxy-2-(N-pyrrolidino)-N-pyrimidinyl- or -N-pyrazinolpropylamines useful for treatment of cardiovascular disorders
EP0330910A1 (en) * 1988-02-16 1989-09-06 Kowa Company, Ltd. Propane derivatives
WO2016098128A1 (en) * 2014-12-16 2016-06-23 Council Of Scientific & Industrial Research Process for the preparation of bepridil

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2558159B1 (en) * 1984-01-18 1986-06-13 Cerm Cent Europ Rech Mauvernay 3-ALKOXY 2- (N-PYRROLIDINO) -N-PYRIDYL-N-ARYLMETHYL-PROPYLAMINES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
DE3726632A1 (en) * 1987-08-11 1989-05-18 Boehringer Mannheim Gmbh 1,2-DIAMINO COMPOUNDS, METHOD FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
DE3726633A1 (en) * 1987-08-11 1989-02-23 Boehringer Mannheim Gmbh NEW 1,2-DIAMINO COMPOUNDS, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE795735A (en) * 1972-03-06 1973-06-18 Cerm Cent Europ Rech Mauvernay NEW ETHYLENEDIAMINES SUBSTITUTES WITH CARDIOVASCULAR ACTIVITY

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0096720A1 (en) * 1981-12-28 1983-12-28 Carter Wallace Process for the preparation of B-[(2-methylpropoxy)-methyl]-N-phenyl-N-(phenylmethyl)-1-pyrrolidineethanamine.
EP0096720A4 (en) * 1981-12-28 1984-05-29 Carter Wallace Process for the preparation of B-[(2-methylpropoxy)-methyl]-N-phenyl-N-(phenylmethyl)-1-pyrrolidineethanamine.
AU569326B2 (en) * 1983-09-27 1988-01-28 Riom Laboratoires C.E.R.M. "Rl-Cerm" S.A. 2-(n-pyrrolidino)-3-isobutoxy-n-substituted phenyl-n-benzyl-propylamines
AU568694B2 (en) * 1983-11-11 1988-01-07 Akzo N.V. N-benzyl-n-phenyl-b-pyrrolidinyl-f-isobutoxy-propylamine
AU568704B2 (en) * 1983-11-11 1988-01-07 Akzo N.V. Ether of n-propanolamine derivative
US4555514A (en) * 1984-01-18 1985-11-26 Riom Laboratoires C.E.R.M. "Rl-Cerm" S.A. 3-Alkoxy-2-(N-pyrolidino)-N-pyridyl-N-furyl(or thienyl) methyl-pyropyl amines useful as calcium antagonists
US4762834A (en) * 1984-01-18 1988-08-09 Riom Laboratoires C.E.R.M. "Rl-Cerm", S.A. 3-alkoxy-2-(N-pyrrolidino)-N-pyrimidinyl- or -N-pyrazinolpropylamines useful for treatment of cardiovascular disorders
EP0330910A1 (en) * 1988-02-16 1989-09-06 Kowa Company, Ltd. Propane derivatives
WO2016098128A1 (en) * 2014-12-16 2016-06-23 Council Of Scientific & Industrial Research Process for the preparation of bepridil

Also Published As

Publication number Publication date
PT67556B (en) 1979-06-18
PT67556A (en) 1978-02-01
NL189258B (en) 1992-09-16
BE863214A (en) 1978-07-24
JPS5392764A (en) 1978-08-15
FR2378024B1 (en) 1979-05-11
AU516479B2 (en) 1981-06-04
IL53816A0 (en) 1978-04-30
NL189258C (en) 1993-02-16
ZA78426B (en) 1979-01-31
NL7800753A (en) 1978-07-27
CH628889A5 (en) 1982-03-31
FR2378024A1 (en) 1978-08-18
DE2802864A1 (en) 1978-07-27
ES466237A1 (en) 1978-10-16
DE2802864C2 (en) 1982-12-09
JPS5429493B2 (en) 1979-09-25
AU3266078A (en) 1979-08-02

Similar Documents

Publication Publication Date Title
DE69204906T2 (en) 2-Hydroxy-2-phenylethylamine derivatives as beta-3-adrenoceptor agonists.
US5352703A (en) Antitussive and mucus regulating agent, a process for the preparation thereof and pharmaceutical compositions containing it
US4220649A (en) 1,4-Dihydropyridine-3,5-dicarboxylic acid ester derivatives
IE49701B1 (en) Amides of acyl-carnitines,process for preparing same and pharmaceutical compositions containing such amides
US4330677A (en) Polyether compounds, their production and their medicinal use
US4250183A (en) N-(Substituted amino)alkanoyl-aminoalkanoic acids and salts, their use and their compositions
JPS6323186B2 (en)
HU184966B (en) Process for producing phenyl-piperazine derivatives of anti-agression activity
US4110470A (en) Pharmaceutical composition comprising d,l-α-methyl-thyroxine ethyl ester and the salts thereof and the control of cholesterol and triglyceride blood level therewith
US3639477A (en) Novel propoxyguanidine compounds and means of producing the same
GB1595031A (en) 3-isobutoxy-2-pyrrolidino-n-phenyl-n-benzyl propylamine and its salts
JPS6314702B2 (en)
JPS6242905B2 (en)
US4000193A (en) Pharmacologically active compounds
US5082856A (en) Pyrrolecarboxylic acid derivatives
US4757062A (en) Substituted benzoate ester prodrugs of estrogens
US5451606A (en) Anthraquinone compounds useful to treat osteoarticular conditions, pharmaceutical compositions and method of treatment
USRE35096E (en) Pyrrolecarboxylic acid derivatives
JPS5826886A (en) Piperazine derivative of theobromine, manufacture and medicinal composition containing same
US4530843A (en) Isoindole amidoxime derivatives
CN116478050B (en) Chiral aryl propionic acid derivative, and pharmaceutical composition and application thereof
US4464379A (en) Indol acetic acid derivatives and anti-inflamatory and related uses thereof
US4338319A (en) Method for the treatment of chronic obstructive airway or cardiac diseases
EP0047358B1 (en) Indol acetic derivatives, process for producing the same and pharmaceutical compositions comprising the same
US4192883A (en) Amides of pyrrolidinoethylamine which can be used in lung therapy

Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
732 Registration of transactions, instruments or events in the register (sect. 32/1977)
704A Declaration that licence is not available as of right for an excepted use (par. 4a/1977)
PE20 Patent expired after termination of 20 years

Effective date: 19980112