IE861925L - N-oxides of n,n-dimethyl ethylamine. - Google Patents

N-oxides of n,n-dimethyl ethylamine.

Info

Publication number
IE861925L
IE861925L IE861925A IE192586A IE861925L IE 861925 L IE861925 L IE 861925L IE 861925 A IE861925 A IE 861925A IE 192586 A IE192586 A IE 192586A IE 861925 L IE861925 L IE 861925L
Authority
IE
Ireland
Prior art keywords
oxyde
pharmaceutical compositions
examples
hereinbefore described
dimethyl
Prior art date
Application number
IE861925A
Other versions
IE58999B1 (en
Original Assignee
Rolland Sa A
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from FR8515448A external-priority patent/FR2588552B3/en
Application filed by Rolland Sa A filed Critical Rolland Sa A
Publication of IE861925L publication Critical patent/IE861925L/en
Publication of IE58999B1 publication Critical patent/IE58999B1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C291/00Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00
    • C07C291/02Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
    • C07C291/04Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds containing amino-oxide bonds

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  • 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 [EP0216646A2]

Description

58999 f This invention relates to a novel derivative of NN-dimethyl ethylamine and more particularly to an N-oxyde* ;This invention specifically provides the M-oxyde of 2 p 2-bis phenoxy MN-dimethyl ethyl ami Be having the formula ;This invention also relates to the salts of M-oxyde with a mineral or organic acid and more precisely with a strong acid as hydrochloric acide, hydrohromic acid or sulphuric acid. ;The N-oxyde of 2,, 2-bis phenoxy NN-dimethyl ethylamine is a 10 weak base and leads to acid addition salts only with non-reducing strong acids. ;The N«oxyde and. the salts thereof are prepared according to a process which consists to react 2,2-bis phenoxy NM-dimethyl ethylamine or a salt thereof with a mineral or organic 15 peroxyde in an inert solvent. Preferablyf the peroxyde is perhydrol. It may also be a hydroperoxide 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. ;20 The solvent of the reaction medium is an inert solvent such as methanol, ethanol or an aromatic hydrocarbon such as toluene ;- 3 - ;or xylol or a NM-disubstituted lower alkylamide such as dimethyl formamide or dimethyl acetamide. ;2 £ 2-bis phenoxy MM-dime thy1ethy1amiBe M-oxyde and its salts show the characteristic properties of the conation anti-5 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 antagonize the dispair test in the mice. ;10 2,2-bis phenoxy OT-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 MM-dimethy1ethy1amine have been described as having anti-depressant activities. The testing performed by the 15 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 20 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 M~oxyde presents an antagonistic action in the test of apomorphine ? and a positive action against the group 25 toxicity with yohimbine clearly more marked than those shown by 2 £, 2-bis phenoxy KB -d ime thy 1 ethy 1 amine „ 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 30 equivalency existing between a M-acylated pentane diamine and its M-oxyde. It may merely be stated that in a 'juite ;- 4 - ;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 2 e2-bis phenoxy NN- ;s dimethyl ethylamine and its K- oxyde possess very different ;I 5 pharmacological properties. It appears to be frequent in the literature to notice that a H-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 10 the case of bis phenoxy MM-dimethyl ethylamine, not only the N-oxyde subject matter of this invention is much less toxic f but in addition e it is markedly more active than the starting tertiary amine. ;Due to their anti-depressive properties £, they found an use in 15 human or veterinary medicine in the treatment of depressive condition e of the involuting psychoses, of the maniaco-depressive 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 20 without fear of side-effects (such as dryness of the mouthe 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, 25 namely to produce tablets, coated tablets f dragees, soft gelatine capsules, capsulesc, drops£, injectable or drinkable solutionsi preparations for percutaneous applications. ;The following examples are merely intended for illustrating ^ the invention. They do not limit it in any manner. ;\ ;.1 ;_ 5 - ;BX38JHPI.B 1 ;Preparation of the N-oxyde of 2 £, 2-bis phenoxy MM-dimethyl ethylamine. ;- In a three-neck flask of 100 ml fitted with a decantation 5 funnela thermometer,, a cooling devicee, 5,15 g (0t,02M) of M-dimethyl-2? 2-bis phenoxy ethylamine previously dissolved in 50 ml methanol are introduced to which 6 ml 30% - perhyd.ro 1 are dropwise added. After completion of the addition„ stirring at room temperature is kept for 30 ran then the mixture is heated 10 at about 35 0 for 12 hours. ;Finally methanol is distilled off and water is discarded by anisotropic 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 MM-dimethyl which 15 melts at 104°C. The yield amounts to 56,5 % ;Rf = 0,14 (CHCI3/CH3OH 9x1) ;NMR: (CDCL3) 10H (m, 6,8-7,3) ;1H (t; 6,7) ;2H (d; 3,7) ;20 6H (s; 3,2) ;MMR: (CDCL3) of MEDIFOXAMINE 10H (m; 6,8-7,3) ;1H (t; 5,8) ;2H (dp 2,8) 25 6H (s; 2,32). ;EE&MjpjLE II ;Study of the pha:onaco 1 ogica3. characteristics of the M-cxyde of 2, 2 bis phenoxy SN-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.Oo ;100 P.O. 50 P.O. ;100 ;DESPAIR TEST ;p7T| \ too p.o.■■ | | ;«- ;i%T"J ;f\ ;MEDIFOXAMINE ;ch — on — ;-an ;*CHj 600 0/10 700 3/10 300 5/10 + 2°5 + ri + 0"S 5/tO 60% N-OXYDE CHj ch j 500 0/10 1000 1/10 + 2° + 0°7 + J°8 7/10 51% TABLE I 7

Claims (5)

1.CLAIMS
2. 5 2.
3. 10
4. 15 5. 6. 20 The N-oxyde of 2,2 -bis phenoxy NN-dimethyl ethylamine of the formula The acid addition salts of the N-oxyde of claim 1 with a mineral or organic acid. 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 organic peroxyde in an inert medium. 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-f.oxic pharmaceutically-acceptable carrier or vehicle. 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. The pharmaceutical compositions according to any of claims 4 or 5 in which the content of active ingredient ranges from 0.05 g to 0.5 g per unit dosage. A compound substantially as hereinbefore described with reference to the Examples. 3 - 8 - 8. A process substantially as hereinbefore described with reference to the Examples. 9. A composition substantially as hereinbefore described with reference to the Examples.
5. Dated this 21st day of July, 1986 CRUICKSHANK & CO. Agents for the Applicant 1 Holies Street Dublin 2 mm\a:rt5\821S.iiJl
IE192586A 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 IE58999B1 (en)

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 true IE861925L (en) 1987-01-22
IE58999B1 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)

* Cited by examiner, † Cited by third party
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
KR870001153A (en) * 1985-07-22 1987-03-11 데. 롤랑 Pharmaceutical composition containing diphenoxyethylamine derivative and its production method
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)

* Cited by examiner, † Cited by third party
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
KR870001153A (en) * 1985-07-22 1987-03-11 데. 롤랑 Pharmaceutical composition containing diphenoxyethylamine derivative and its production method

Also Published As

Publication number Publication date
IE58999B1 (en) 1993-12-15
AU6038586A (en) 1987-01-29
KR940011528B1 (en) 1994-12-20
KR870001144A (en) 1987-03-11
AU593562B2 (en) 1990-02-15
DE3674873D1 (en) 1990-11-15
EP0216646A3 (en) 1987-11-04
EP0216646B1 (en) 1990-10-10
EP0216646A2 (en) 1987-04-01

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