IE58999B1 - Novel N-oxyde of NN-dimethyl ethylamine, a process for it's production and the pharmaceutical compositions containing it - Google Patents
Novel N-oxyde of NN-dimethyl ethylamine, a process for it's production and the pharmaceutical compositions containing itInfo
- Publication number
- IE58999B1 IE58999B1 IE192586A IE192586A IE58999B1 IE 58999 B1 IE58999 B1 IE 58999B1 IE 192586 A IE192586 A IE 192586A IE 192586 A IE192586 A IE 192586A IE 58999 B1 IE58999 B1 IE 58999B1
- Authority
- IE
- Ireland
- Prior art keywords
- oxyde
- pharmaceutical compositions
- dimethyl ethylamine
- ethylamine
- dimethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000003981 vehicle Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 3
- 229960004046 apomorphine Drugs 0.000 description 3
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 231100001231 less toxic Toxicity 0.000 description 3
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 3
- 229960000317 yohimbine Drugs 0.000 description 3
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 2
- IMLAIXAZMVDRGA-UHFFFAOYSA-N 2-phenoxyethanamine Chemical compound NCCOC1=CC=CC=C1 IMLAIXAZMVDRGA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 2
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003001 depressive effect Effects 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- QNMGHBMGNRQPNL-UHFFFAOYSA-N medifoxamine Chemical compound C=1C=CC=CC=1OC(CN(C)C)OC1=CC=CC=C1 QNMGHBMGNRQPNL-UHFFFAOYSA-N 0.000 description 2
- 229960003123 medifoxamine Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 2
- 229960003147 reserpine Drugs 0.000 description 2
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- KJOMYNHMBRNCNY-UHFFFAOYSA-N pentane-1,1-diamine Chemical class CCCCC(N)N KJOMYNHMBRNCNY-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C291/00—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00
- C07C291/02—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
- C07C291/04—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds containing amino-oxide bonds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
1. 2,2-bis phenoxy NN-dimethylethylamine N-oxyde having the formula see diagramm : EP0216646,P5,F3
Description
This invention relates to a novel derivative of NN-dimethyl ethylamine and more particularly to an N-oxyde.
This invention specifically provides the N-oxyde of 2,2-bis phenoxy NN-dimethyl ethylamine having the formula This invention also relates to the salts of N-oxyde with a mineral or organic acid and more precisely with a strong acid as hydrochloric acid, hydrobromic acid or sulphuric acid.
The N-oxyde of 2,, 2-bis phenoxy NN-dimethyl ethylamine is a weak base and leads to acid addition salts only with nonreducing strong acids.
The N-oxyde and the salts thereof are prepared according to a process which consists to react 2,2-bis phenoxy NN-dimethyl ethylamine or a salt thereof with a mineral or organic peroxyde in an inert solvent. Preferably, the peroxyde is perhydrol. It may also be a hydroperoxyde from an alkanol such as tert-butyl peroxyde; a hydroperoxyde from a ketone such as hexafluoro acetone peroxyde; a peracid such as p.nitroperbenzoic acid or 4-chloroperbensoic acid.
The solvent of the reaction medium is an inert solvent such as methanol, ethanol or an aromatic hydrocarbon such as toluene or xylol or a NN-disubstituted lower alkylamide such as dimethyl formamide or dimethyl acetamide. 2£ 2"bis phenoxy MN^dimethylethylamine M-oxyde and its salts show the characteristic properties of the common anti5 depressive agents on the classical pharmacological tests. They inhibit the hypothermizing effect of Reserpine and Apomorphine. They increase the group toxicity induced by injection of yohimbin and they antagonise the dispair test in the mice. 2,2-bis phenoxy NN-dimethylethylamine has already been disclosed in the literature as well as its salts (see French brevet special de Medicament 5498M). The salts of 2£, 2-bis phenoxy NN-dimethyTethylamine have been described as having anti-depressant activities. The testing performed by the applicant has evidenced the fact that these compounds show a significative acute toxicity in the mice which allows to locate the mean lethal doses to 800mg/kg.
In contrast thereof the N-oxyde which is the subject matter of this application shows a very weak toxicity while keeping about the same level of activity and consequently it has not been possible to determine at doses acceptable for the animals, a mean lethal doses.
Moreover j, the N-oxyde presents an antagonistic action in the test of apomorphine, and a positive action against the group toxicity with yohimbine clearly more marked than those shown by 21,2-bis phenoxy NN-dimethylethylamine. In other words , the M-oxyde is more active than the prior art compound from which it derives, while being clearly less toxic.
The French patent 2 , 384 £-495 has been cited to show the equivalency existing between a N-acylated pentane diamine and its N-oxyde. It may merely be stated that in a quite 1' different chemical family, the two kinds of compounds behave in pharmacology in a similar fashion. In contrast thereof, in the series of bis phenoxy ethylamine, the 2t2bis phenoxy NNdimethyl ethylamine and its oxyde possess very different pharmacological properties. It appears to be frequent in the literature to notice that a N-oxyde is less toxic or possess about the same level of toxicity that the tertiary amine, from which it derives, but this decrease is also the result of a lowering of the pharmacological activity in the animals. In the case of bis phenoxy NN-dimethyl ethylamine, not only the N-oxyde subject matter of this invention is much less toxic, but, in addition, it is markedly more active than the starting tertiary amine.
Due to their anti-depressive properties, they found an use in human or veterinary medicine in the treatment of depressive condition, of the involuting psychoses, of the maniacodepressive states, of the depressions of reaction or behaviour. These molecules being very weakly toxic, their therapeutical margin is very extended and they may be given without fear of side-effects (such as dryness of the mouth, extrapyramidal disturbances) which may occur with the antipressant drugs belonging to the tricyclic group.
The production of these pharmaceutical compositions is carried out according to the known methods of pharmacotechnology, namely to produce tablets, coated tablets, dragees, soft gelatine capsules, capsules, drops, injectable or drinkable solutions, preparations for percutaneous applications.
The following examples are merely intended for illustrating the invention. They do not limit it in any manner.
EZaWLE. 1 Preparation of the N-oxyde of 2,2-bis phenoxy NN-dimethyl ethylamine.
- In a three-neck flask of 100 ml fitted with a decantation 5 funnel, a thermometer, a cooling device, 5,15 g (0,02M) of NNdimethyl-2,2-bis phenoxy ethylamine previously dissolved in 50 ml methanol are introduced to which 5 ml 30% - perhydro 1 are dropwise added. After completion of the addition, stirring at room temperature is kept for 30 mn then the mixture is heated at about 35 0 for 12 hours.
Finally methanol is distilled off and water is discarded by azeotropic distillation with ethanol. The residual oily residue is taken up in ether; a white solid matter appears. After filtration and drying 3.08g N-oxyde of NN-dimethyl which melts at 104°C. The yield amounts to 56,5 % Rf = 0,14 (CHCI3/CH3OH 9sl) NMR: (CDCL3) 10H (m, 6,8-7,3) IH (t; 6,7) 2H (d; 3,7) SH (s; 3,2) NMR: (CDCL3) of MEDIFOXAMINE 10H (m; 6,8-7,3) IH (t; 5,8) 2H (d; 2,8) 25 6H (s? 2,32).
EXAMPLE II Study of the pharmacological characteristics of the N-oxyde of 2,2 bis phenoxy NN-dimethyl ethylamine, see Table I - 6 EXAMPLE II Pharmacological study on 2,2-bis phenoxy NN-dimethyl ethylamine N-oxyde PRODUCT CHEMICAL STRUCTURE ACUTE TOXICITY HYPOTHERMIA HYPOTHERMIA TOXICITY TO ON MICE TO RESERPINE TO APOMORPHINE YOHIMBINE p„O„ | 100 P.O.| j 50 P.O.j | 100 P.O, | t WO· P.O. ] DESPAIR TEST N-OXYDE MEDIFOXAMINE CHi • CHs 'CHs 600 0/10 700 3/10 300 5/10 + 2’5 + Γ1 + 0°3 /10 60% 500 0/10 1000 1/10 + 2° £ 0°7 + !e6 7/SO « 51% s TABLE I
Claims (7)
1. The N-oxyde of
2. ,2 -bis phenoxy NN-dimethyl ethylamine of the formula 5 2. The acid addition salts of the N-oxyde of claim 1 with a mineral or organic acid.
3. A process for producing the N-oxyde of claim 1 in which a 2,, 2-bis phenoxy NN-dimethyl ethylamine or an acid addition salt thereof is reacted with a mineral or 10 organic peroxyde in an inert medium.
4. The pharmaceutical compositions having as active ingredient a compound according to any of claims 1 or 2 in combination or admixture with an inert non-toxic pharmaceutically-acceptable carrier or vehicle. 15 5. The pharmaceutical compositions according to claim 4 in which the carrier or the vehicle is one of those suitable for parenteral, oral, rectal or percutaneous ways of administration. β. The pharmaceutical compositions according to any of 20 claims 4 or 5 in which the content of active ingredient ranges from 0.05 g to 0.5 g per unit dosage.
5. 7. A compound substantially as hereinbefore described with reference to the Examples. -
6. 8 8. A process substantially as hereinbefore described with reference to the Examples.
7. 9. A composition substantially as hereinbefore described with reference to the Examples.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8511152 | 1985-07-22 | ||
| FR8515448A FR2588552B3 (en) | 1985-10-16 | 1985-10-16 | NOVEL OXIDE DERIVATIVE OF NN-DIMETHYL ETHYLAMINE, PROCESS FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE861925L IE861925L (en) | 1987-01-22 |
| IE58999B1 true IE58999B1 (en) | 1993-12-15 |
Family
ID=26224627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE192586A IE58999B1 (en) | 1985-07-22 | 1986-07-21 | Novel N-oxyde of NN-dimethyl ethylamine, a process for it's production and the pharmaceutical compositions containing it |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0216646B1 (en) |
| KR (1) | KR940011528B1 (en) |
| AU (1) | AU593562B2 (en) |
| DE (1) | DE3674873D1 (en) |
| IE (1) | IE58999B1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2583639B3 (en) * | 1985-06-24 | 1987-09-25 | Rolland Sa A | NOVEL PHARMACEUTICAL COMPOSITIONS IMPROVING PSYCHOMOTOR PERFORMANCE AND PROCESS FOR OBTAINING SAME |
| EP0226475A1 (en) * | 1985-07-22 | 1987-06-24 | Albert ROLLAND S.A. Société dite | Diphenoxyethyl amine derivatives, process for their preparation and pharmaceutical compositions containing them |
| FR2589357B3 (en) * | 1985-11-05 | 1988-01-29 | Rolland Sa A | NOVEL PHARMACEUTICAL COMPOSITIONS IMPROVING CEREBRAL OXYGENATION BASED ON DIPHENOXY DIMETHYLAMINOETHANE AND PROCESS FOR OBTAINING SAME |
| CA2014201A1 (en) * | 1989-04-26 | 1990-10-26 | Albemarle Corporation | Solid non-hygroscopic trialkylamine oxides |
| US5866718A (en) * | 1997-03-20 | 1999-02-02 | General Electric Company | Synthesis of tertiary amine oxides |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5498M (en) * | 1966-05-18 | 1967-10-30 | ||
| DE2749214A1 (en) * | 1976-11-30 | 1978-06-01 | Upjohn Co | N- (2-AMINOCYCLOPENTYL) -N-ALKANOYLANILIDE OR THE 2-N-OXIDES THEREOF, METHOD FOR THEIR PREPARATION AND USE OF THE SAME IN THE TREATMENT OF DEPRESSIVE CONDITIONS |
| EP0226475A1 (en) * | 1985-07-22 | 1987-06-24 | Albert ROLLAND S.A. Société dite | Diphenoxyethyl amine derivatives, process for their preparation and pharmaceutical compositions containing them |
-
1986
- 1986-07-21 IE IE192586A patent/IE58999B1/en not_active IP Right Cessation
- 1986-07-21 AU AU60385/86A patent/AU593562B2/en not_active Ceased
- 1986-07-22 DE DE8686401630T patent/DE3674873D1/en not_active Expired - Fee Related
- 1986-07-22 KR KR1019860005928A patent/KR940011528B1/en not_active Expired - Fee Related
- 1986-07-22 EP EP86401630A patent/EP0216646B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0216646A3 (en) | 1987-11-04 |
| EP0216646B1 (en) | 1990-10-10 |
| AU593562B2 (en) | 1990-02-15 |
| DE3674873D1 (en) | 1990-11-15 |
| EP0216646A2 (en) | 1987-04-01 |
| KR870001144A (en) | 1987-03-11 |
| KR940011528B1 (en) | 1994-12-20 |
| IE861925L (en) | 1987-01-22 |
| AU6038586A (en) | 1987-01-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0026848B1 (en) | Derivatives of tetraline, their preparation and medicaments containing these compounds | |
| JPH02138238A (en) | Benzylidene- and cinnamylidene-malononitrile derivative, preparation thereof and drug composition containing it as active ingredient and for suppressing proliferation in mammal cell | |
| AU581285B2 (en) | Piperazinecarboxamides | |
| CA2489396A1 (en) | Utilization of heteroarene carboxamide as dopamine-d3 ligands for the treatment of cns diseases | |
| IE58999B1 (en) | Novel N-oxyde of NN-dimethyl ethylamine, a process for it's production and the pharmaceutical compositions containing it | |
| US2991290A (en) | Nu-alkylamino-alpha-hydroxy-alkanoic acid amides | |
| EP0200942B1 (en) | New derivatives of an aminoketone | |
| Rokach et al. | Cyclic amidine inhibitors of indolamine N-methyltransferase | |
| US3015657A (en) | 1-carbalkoxy-4-(aminoalkanol) piperazines | |
| JPH04501263A (en) | Novel 4-methyl-5-[2-(4-phenylpiperazin-1-yl)ethyl]thiazole derivatives, methods for their production and pharmaceutical compositions containing them | |
| HU215436B (en) | Process for the preparation of N - [(4,5-dihydroxy-9,10-dihydro-9,10-dioxo-2-anthracenyl) carbonyl] amino acids and pharmaceutical compositions containing such an active ingredient. | |
| US5229412A (en) | Method for relieving anxiety using 5-hydroxytryptamine-1a-receptor-binding compounds | |
| CH627175A5 (en) | ||
| US3337562A (en) | Substituted 2-pyrrylketones | |
| US3465080A (en) | Therapeutic compositions containing morpholinoalkylene - indoles and methods of administering such in the treatment of depression | |
| US5091429A (en) | Derivatives of 4-amino-1-trifluoromethyltetralines their preparation and their therapeutic application | |
| JP2004511548A (en) | Method for preparing N-substituted 2-sulfanilimidazole | |
| US2569814A (en) | beta-haloethylamines | |
| CA1215048A (en) | 2-(hexahydroazepino)-n-(2,6-dimethylphenyl)- acetamide, the hydrochloride thereof, a process for the preparation thereof and pharmaceutical compositions containing them | |
| US2921075A (en) | Carbamidomethyl quaternary salts of tropine | |
| Fitzgerald et al. | Radioprotective activity of p-aminopropiophenone. Structure-activity investigation | |
| KR830000772B1 (en) | Method for preparing isoquinoline derivative | |
| FI64353B (en) | FOERFARANDE FOER FRAMSTAELLNING AV E-3- (4-BROMOPHENYL) -N-METHYL-3- (3-PYRIDYL) -ALLYLAMINE TILL ANVAENDNING SOM LAEKEMEDEL | |
| Kaye et al. | Alkyl Ethers of Basically-substituted 2-Amino-1-phenylethanol1 | |
| Charaf et al. | New β-adrenoceptor-blocking agents derived from dicyclopropyl ketone oxime: influence of amino substituents on in vivo activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |