CA1108163A

CA1108163A - N,n-disubstituted-2-furylethyl amines

Info

Publication number: CA1108163A
Application number: CA268,811A
Authority: CA
Inventors: Jozself Knoll; Zoltan Ecsery; Zoltan Torok; Eva Somfai; Gabor Bernath; Judit Hermann
Original assignee: Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Current assignee: Chinoin Private Co Ltd
Priority date: 1975-12-29
Filing date: 1976-12-29
Publication date: 1981-09-01
Also published as: SE429654B; CS216166B2; FR2336928A1; NL7614474A; DE2658064A1; DE2658064C2; JPS619311B2; AR215610A1; ATA957376A; DD131853A1; DD129327A1; YU314576A; SU932990A3; SU845784A3; SE7614473L; CS216167B2; CH633285A5; PL194802A1; GR62443B; CH630620A5

Abstract

ABSTRACT OF THE DISCLOSURE

This invention relates to novel racemic or optically active N-2-(2-furyl)-ethyl-amine derivatives of the formula I

(I)

Description

~.~8~63 This invention relates to new amines. More particularly it is concerned with new N-2-(2-furyl)-ethyl amine derivatives, a process for the preparation thereof and pharmaceutical compositions comprising the same.
According to an aspect of the present invention there are provided compounds of the formula I

~ Rl R2 (I) O

and pharmaceutically acceptable salts thereof ~wherein Rl and R2 are hydrogen or lower alkyl of 1 to 4 carbon atoms, and R3 is halogenoalkenyl of 2 or 3 carbon atoms, the halogen being chlorine or bromine or propynyl).
It is known that furyl-ethyl amines exhibit a pharmacological ; effect similar to that of phenyl-ethyl amine [J. Pharmacol. 72, 265 /1941/].
The new compounds of the formula I are free of the undesired "amphetamine"
effect, but are capable of selective inhibition of monoaminooxidase. Some known compounds of different chemical structure are described to have selective monoaminooxidase inhibitlng effect. (Biochemical Pharmacology 18, /1969/ 1447; Br. J. Pharmacology 45, /1972/ 490). The said compounds inhibit however mainly the oxidation of 5-hydroxy-triptamine. It is known that N,alpha-dimethyl-N-beta-phenyl-N-propynylamine ~British Patent No.
1,031,425) inhibits the oxidation of benzyl amine (Br. J. Pharmacology 45, 2Q 490 /1972/). The compounds of the formula I possess however more favourable `~ properties, than the phenyl-ethyl-propynyl amine derivatives mentioned above.
The compounds of the formula I possess a chiral carbon atom and ~ may be present either in racemic or in optically active forms. The present :
.. -1- ~

~)8163 invention encompasses hoth the racemic and optically active forms of the compounds of the formula I and the preparation thereof.
The term "lower alkyl group" relates to straight or branched chain alkyl groups having 1-4 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, etc.). The alkyl group may be preferably a methyl group.
The halogenoalkenyl group comprises 2 or 3 carbon atoms and chlorine or bromine as halogen (e.g. bromo-propenyl).
The pharmaceutically acceptable salts of the compounds of the formula I may be formed with inorganic or organic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, maleic acid, tartaric acid, fumaric acid, succinic acid, lactic acid, etc.).
According to a further aspect of the present invention there is provided a process for the preparation of compounds of the formula I

~;~ CH IH I ~3 (I) which comprises a) reacting a compound of the formula l (II) with a compound of the formula III

B - R (III) (wherein Rl, R2 and R3 are as stated above, and A a2nd B stand for groups, R
which on reacting with each other the bivalent - ~ - radical or comprises the said radical) and if required converting a halogeno alkenyl group in the obtained product into a propynyl group; or ~1~8~63 b) reacting a co~pound of the formula ~ ~ R (VI) o CH2 CO
with a compound of the formula V
: 7 3 ~V) HN - R
with simultaneous or subsequent reduction; or c) condensing a compound of the formula IV

l R2 (IV) o C~12 ~ CH - NH
with formaldehyde and acetylene and if required converting a compound of the ; formula I thus obtained into its pharmaceutically acceptable acid addition salt or setting free a compound of the formula I from its acid addition salt and if required separating a racemic compound of the formula I into its optically active isomers.
According to an embodiment of method a) of our process a compound of the formula IV is reacted with a compound of the formula III, wherein R3 is propargyl and B is halogen or a sulfonic acid ester group, e.g. an alkyl-sulfonyloxy or arylsulfonyloxy group, such as chlorine, bromine, benzene-sulfonyloxy, p-toluenesulfonyloxy or methanesulfonyloxy. The reaction may be carried out in a solvent or without solvent. It is preferable to add an ~ acid binding agent to the reaction mixture. As acid binding agent inorganic ; 20 or organic bases, such as alkali or alkali earth metal hydroxides, carbonates or tertiary amines may be used. An excess of the amine of the formula IV may ~` serve as acid binding agent too. In this case one may proceed preferably by using the excess of amine both as acid binding agent and .' .

.

reaction medlum. ~he reaction may be accomplished preferably at a temperature between 20 and 120C. As solvent aliphatic and aromatic hydrocarbons, such as petrol, benzene and its homologues, alkanols ~e.g. ethanol, methanol, butanol, etc.) ketones ~e.g. methyl-ethyl-ketone, cyclohexanone, etc.~ may be used. According to a particularly preferable form of realisation of this reaction variant an amine of the formula IV is dissolved in toluene and propargyl bromide and an aqueous sodium hydroxide solution are added simultaneously dropwise. The reaction is completed by heating if necessary.
The product is recovered from the reaction mixture by addition of an alkali and subsequent extraction. If the ; reaction is carried out in a water-immiscible solvent, it is preferred to remove this solvent by distillation and adding the aqueous sodium hydroxide to the residue. The two-phase mixture is extracted with a water-immiscible solvent (e.g. e~her or benzene), the extract is dried, evaporated and the residue is purified by fractionated distillation.
If the compound of the formula I thus obtained is a tertiary base CR2 is alkyl) the product may be advantageously purified by the acylation of the evaporation residue, In this case the unreacted starting material of the formula ~V Csecondary base) is acylated, the acylated product thus obtained is insoluble in diluted acids and the tertiary base of the formula I can be recovered by extraction with diluted acid in pure form. Acylation may be carried out with conventional acylating agents ~e.g. acid anhydrides or acid chlorides such as acetic anhydride or benzoyl :
~.

X.

' ~

~108163 chloride) in the presence of an alkali. After acylation the reaction mixture is extracted with cold diluted hydrochloric acid, whereupon the acidic extract is made alkaline, the precipitated tertiary amine of the formula I
is extracted with a solvent, dried, evaporated and the residue is distilled off. The product may be converted into a salt formed with an organic or inorganic acid.
According to another embodiment of process a) a compound of the formula IV is reacted with propargyl aldehyde under simultaneous or subsequent reduction. One may proceed by reacting the compound of the formula IV with propargyl aldehyde in a solvent or without solvent. As reaction medium preferably water-immiscible solvents (e.g. benzene and its homologues, such - as toluene, xylene, petrol, etc.) may be usedO In this case the water formed in the reaction is separated and this shifts the reaction equation towards the formation of the Schiff-base. This product is then reduced into ; the corresponding compound of the formula I. One may also proceed by carry-ing out condensation and reduction simultaneously. Reduction may be preferably accomplished with the aid of nascent hydrogen.
According to a further embodiment of method a) a compound of the formula VII

~ Rl CH - CH - X ~VII) (wherein X is halogen or a sulfonic acid radical, e.g. an alkylsulfonyloxy or arysulfonyloxy group, such as chlorine, bromine, methanesulfonyloxy, ., .
..5_, ~1(1 8~3 phenylsulfonyloxy or p-toluenesulfonyloxy) is reacted with an amine of the formula V. The reaction may be carried out in the presence or absence of a solvent. As reaction medium hydrocarbons (e.g. benzene and its homologues, petrol, etc.) alcohols or ketones may be used. An excess of the amine component may serve as reacting medium too. The reaction may be preferably accomplished in the presence of an acid binding agent. For this purpose organic or inorganic bases or an excess of the amine of the formula V may be used. The reaction may be carried out at a temperature between 20 and 130 C. The recovery and purification of the product may be carried out by lQ known physical methods (e.g. extraction, distillation, crystallization).
According to method b) a 2-furyl-acetone of the formula VI

l (VI) o CH2 - CO

is reacted with an amine of the formula V

~IN - R
under simultaneous or subsequent reduction. The reduction may be accomplished preferably with the aid of nascent hydrogen.

.
';
~' ~. ~..

11~8163 According to method c) a compound of the formula IV is reacted with paraformaldehyde and acetylene. The reaction is carried out in an ether of high boiling point (e.g. butylether or dioxane) in the presence of cuprous acetylide. The reaction is performed preferably at a temperature of 80 to 150 C. One may proceed preferably by dissolving the compound of the formula IV in dioxane, adding cuprous acetylide or a compound capable of forming cuprous acetylide (e.g. cuprous - chloride) and introducing ; acetylene into the mixture under heating and stirring. The compound of the formula I may be isolated by methods known per se.
The propynyl group may also be formed by subsequent modification of a halogenopropenyl derivative. Thus one may proceed by reacting a compound of the formula IV with an 1,2-dihalogeno-alkene ~e.g. 1,2-dibromo-propene) and splitting off hydrogen halide from the halogeno-propenyl derivative thus obtained with an alkali hydroxide, alkaline earth metal hydroxide, or an organic base.
The compounds of the formula I thus obtained may be converted into a pharmaceutically acceptable acid addition salt formed with an inorganic or organic acid. The product may also be purified through the salts under utilising the fact that the salts are crystalline, readily crystallisable substances. After purification the base is set free from the salt by treatment with an alkali. For salt-formation hydrochloric acid, hydro-.

~7-: .

~1~81G3 bromic acid, sulfuric acid, phosphoric acid, maleic acid, lactic acid, citric acid, scorbic acid, etc. may be used.
Compounds of the formula I in which Rl is an alkyl group contain a chiral carbon atom and may exist in racemic or optically active forms. The racemate may be subjected to resolution by conventional method The optically active compound of the formula I may also be prepared by using an optically active amine of the formula IV in the reactions a) and b).
According to a further feature of the present invention there are provided pharmaceutical compositions comprising as active ingredient a compound of the formula I or its salt in admixture with suitable inert solid or liquid carriers or diluents. The compositions may be finished in solid (e.g. tablets, pills, coated pills, capsules, dragées, powder mixtures) or liquid ~e.g. aqueous solution or suspension~ forms. The ~ ~-compositions are suitable for oral, or parenteral administration. The compositions contain conventional carriers, e.g. talc, calcium carbonate, magnesium stearate, water, vaseline, polyalkylene glycols, etc. The compositions are prepared by methods of pharmaceutical industry known per se.
The N-methyl-N-~2-~furyl-2)-ethyl~-propynyl amine in an in vivo dose of 6.25 mg./kg. inhibits ln the liver the oxidation of benzyl amine to an extent o 19% and the oxidation of thyramine only by 44%.
In a dose of 5 mg./kg. N-methyl-N-~l-methyl-2-~furyl-2)-ethyl]propynyl amine inhiblts in the brain the oxidation of benzylamine to an extent of 53% and that of 5-hydroxy-triptamine only 2%. On the other hand the known compound N,alpha-dimethyl-N-beta-phenyl-ethyl-N-propynyl-amine shows in the same dose an inhibition of 80% of the oxidation of benzylamine in the brain, while the inhibition of the oxidation of 5-hydroxy-triptamine is 15%. The said known phenyl derivative when administered in a dose of l0 mg/kg. inhibits the oxidation of benzylamine in the liver by 78%, and ; the oxidation of 5-hydroxy triptamine by 56%. The above data show that the compounds of the formula I exhibit a more selective monoaminooxidase , X~

~1~)8~63 inhibiting effect, than the known phenyl derivatlves. According to in vitro tests the selectivity is more pronounced.
The reserplne depression antagonising antldepressive effect of the compounds of the formula I ls significantly stron~er than that of the phenyl analogues.
The toxicity of the compounds of the formula I is smaller, than that of the known phenylderlvativesJ and therefore the new compounds of the present invention possess a more advantageous therapeutical index and a broader spectrum of activity.
Further details of the present invention are to be found in the Examples without llmiting the scope o our invention to the Examples.
Example 1 -~ ~
7.9 g. ~0.0568 moles) of N-methyl-N-[l-methyl-2-~furyl-2)-ethyl]-; amine are dissolved in 142 ml. of toluene, whereupon at 45 to 50C 6.7 g~
~0.0568 moles) of propargyl bromide and 11.4 ml. of a 5 N aqueous sodium hydroxide solution are added at the same time under stirring. The reaction mixture is refluxed under stirring for 3 hours. After cooling 14.8 ml. of a 10 N sodium hydroxide solution are added and the phases are separated.
The aqueous layer is extracted twice with benzene, whereupon the benzene - 20 and toluene solutions are united, dried over anhydrous potassium carbonate and evaporated. The residue is dissolved in 50 ml. of ben~ene and refluxed with 6 g of acetic anhydride for an hour. After cooling the solution is washed with a 20% sodium carbonate solution until the evolution of carbon dioxide ceases. The mixture is washed with water and extracted with 5%
hydrochloric acid at 0C. The hydrochloric acid solutions are united, the mixture is allowed to stand at a temperature below 10C, and made alkaline The separated oil is extracted with ether, the ether extract is dried over potassium carbonate and evaporated. On subjecting the residue to vacuum distillation 6.5 g. of N-methyl-N-[l-methyl-2-~furyl-2)-ethyl]-propynyl-amine are obtained. Bp.: 115-117 C/20 Hgmm; n20 = 1.4922.
Example 2 The process according to Example 1 is carried out except that 1108~63 12.5 g. of N-methyl-N-2-Cfuryl-2)-ethyl amine 11.9 g. ~0.1 mole) of propargyl bromide are reacted in 70 ml. of toluene and 20 ml. of a 5 N
sodium hydroxide solution. Thus 11.2 g. of N-methyl-N-[2-~furyl-2)-ethyl]-propynyl amine are obtained. Bp.: 105-106 C/20 Hgmm; nD = 1.4891. The melting point of the hydrochloride amounts to 106-108C tfrom a mixture of ethanol and ether).
Example 3 To 13.9 g. (0.1 mole) of N-methyl-N-~l-methyl-2-~furyl-2)-ethyl]
amine 10 g. ~0.05 moles) of lJ2-dibromo-propene are added dropwise, the reaction mixture is heated at 100C for 7 hours, whereupon it is cooled to room temperature and dissolved in 5% hydrochloric acid. The acidic solution is extracted with ether and made alkaline with 40% sodium hydroxide.
The precipitated oil is extracted with ether, the extract is dried and evaporated. To the residual brown oil 60 ml. of 40% sodium hydroxide and 30 ml. of benzoyl chloride are added parallelly dropwise within 30-45 minutes in order to benzoylate the unreacted N-methyl-N-[methyl-2-~furyl-2)-ethyl] amine. During the addition the temperature of the reaction mixture rises to 50-60C. The addition having been completed the reaction mixture is stirred at this temperature for an hour, whereupon it is cooled to room ; 20 temperature and benzene is added. The mixture is shaken and the benzene phase is separated and extracted with 5% hydrochloric acid. The N-methyl-N-il-methyl-2-tfuryl-2)-ethyl~-N-2-bromo-propenyl amine dissolves in the acidic phase, while the N-methyl-N-[l-methyl-2-~furyl-2)-ethyl]-benzoyl amlne remains in the benzene solution. The hydrochloric acid layer is made alkaline, the precipitated N-methyl-N-[l-methyl-2-~furyl-2)-ethyl]-N-2-bromo-propenylamine is extracted with benzene, dried and evaporated.
The residue is disti~led off in vacuo. Thus 7.1 g. of N-methyl-N-[l-methyl-

2-(furyl-2)-ethyl~-N-2-bromo-propenyl amine are obtained. The product is dissolved in 100 ml. of ethanol and 14 ml. of an 50% aqueous potassium hydroxide solution are added. The reaction mixture is refluxed for 16 hours, whereupon the ethanol is distilled off and the residue is admixed with water and extracted with benzene. The benzene solution is dried over anhydrous a~

11~)8~63 potassium carbonate and evaporated. The residue ls distilled off in vacuo. Thus 4.9 g. of N-methyl-N-~l-methyl-2-C2-furyl)-ethyl]-propynyl amine are obtained. Bp.: 114-115 C/20 Hgmm; nD = 1.4915.
Example 4 12.4 g. ~0.1 mole) of N-methyl-N-2-C2-furyl)-ethyl amine are reacted with 10 g. t0.05 moles) of 1,2-dibromo-propene according to ~- Example 3. Thus 7.6 g. of N-methyl-N-~2-C2-furyl)-ethyl~-2-bromo-propenyl amine are obtained, which is reacted with 14 ml. of 50% aqueous potassium hydroxide in 100 ml. of ethanol under heating to boiling as described in Example 3. Thus 5.1 g. of N-methyl-N-C2-~2-furyl)-ethyl~-propynyl amine are obtained. Bp.: 105-106 C/20 Hgmm; n~ = 1.4890. The melting polnt of the hydrochloride amounts to 107-108 C ~from a mixture of ethanol and ether).
~ Example 5 `i 12.4 g. ~0.1 mole) of 2-furyl-acetone are dissolved in 100 ml.
of ethanol, whereupon 7.25 g. ~0.105 moles) of methyl-propynyl amine are added. 3.5 g. of aluminium foil is degreased with ethanol and thereafter activated with a solution of 1 g. of mercuric chlorlde and 15 g. of sodium chloride in 30 ml. of water. The activating solution is decanted after 6-8 minutes and the activated aluminium foil is washed with cold water and added to the alcoholic solution previously prepared under stirrlng.
An exothermic reaction takes place and the temperature is kept at 15 to 30 C by cooling. The reaction mixture is stirred ~or 24 hours, whereupon 30 ml. of 40% sodium hydroxide are added. The two phases are separated/
the lower aqueous phase is extracted three-times with benzene. The benzene solutions are united with the previously separated alcoholic phase and evaporated. The residue consists of an organic oily layer and an a~ueous phase which is extracted with benzene and the benzene so]ution is dried over potassium carbonate. The benzene is removed and the residue is distilled off in vacuo. Thus 6.7 g. of N-methyl-N-[l-methyl-2-~2-~uryl)-;; ethyl]-propynyl amine are obtained. Bp.: 113-115 C/20 Hgmm; nD = 1.4905.

~' - 11 -: ' ` ., .

Example 6 13.9 g. ~0.1 mole) of N-methyl-N-~l-methyl-2-~2-furyl)-ethyl]
aminc and 7 g. ~.184 moles) of propargyl aldehyde are reacted in 100 ml.
of ethanol in the presence of 3.5 g. of aluminium foils as described in Example 5. Thus 6.1 g. of N-methyl-N-~l-methyl-2-t2-furyl)-ethyl]-propynyl amine are obtained. Bp.: 114-llS ~C/20 ~Igmm; nD = 1.4910.
Example 7 13.9 g. ~0.1 mole~ of N-methyl-N-~l-methyl-2-~2-furyl)-ethyl~
amine are dissolved in 80 ml. of dioxane, whereupon 6 g. of paraformaldehyde and 1 g. of cuprous chloride are added and gaseous acetylene is introduced into the solution at 80C under stirring for 30 hours. The reaction mixture is filtered and the filtrate is evaporated. I'he residue is d.issolved in benzene, the benzene solution is washed with water, dried over potassium carbonate and evaporated. The residue is distilled off in vacuo. Thus 6.8 g. of N-methyl-N-Cl-methyl-2-t2-furyl)-ethyl~-propynyl amine are obtained.
Bp.: 114-116 C/20 Hgmm; nD = 1.4910.
Example 8 12.8 g. ~0.1 mole) of 1-methyl-2-~2-furyl-ethyl)-chloride and 15 g.
(0.208 moles) of methyl-propynyl amine are heated in a sealed bomb tube at 70 to 80 C for 4 hours. The reaction mixture is cooled, 30 ml. of 40%
sodium hydroxide are added and the mixture is extracted with benzene. The benzene solution is dried, evaporated and the residue is distilled off in vacuo, Thus 9.8 g. of N-methyl-N-~l-methyl-2-t2-furyl)-ethyl~-propynyl ~mine are obtained. Bp.: 113-115 C/20 ~gmm; nD = 1.4904.
Example 9 11.45 g. ~0.1 mole) of 2-furyl-ethyl-chloride are reacted with 15 g. ~0.208 moles) of methyl-propynyl amine according to the method described in Example 8. Thus 8.8 g. of N-methyl-N-~2-~furyl-2)-ethyl]-propynyl amine are obtained. Bp.: 104-105 C/20 ~gmm; nD = 1.4868.

'li~8163 ~ S~, pp I e~7~n fa ~ ~,s c ~ sc~ ve Example 10 12.5 q. (0.1 mole) of 1-methyl-2-(furyl-2)-ethylamine are dissolved in 70 ml. of dioxane and 6 g. of paraformaldehyde and 1 g. of copper(I) chloride are added to the solution whereupcn acetylene is added, as described in Example 7, and the obtained solution is processed as in Example 7. 6.3 g.
of N-[l-methyl-2-(furyl-2)-ethyl]-propynylamine are obtained. Bp.: 55-60 C/5 Hgmm; nD = 1.4895; hydrochloride salt; Mp.: 107-111 C. Analysis on the basis of the formula CloH13N0 HCl ~ calculated: C 60.15%; H 7.06%; N 7.01%; Cl 17.75%;
: 10 found: C 60.39%; ~ 7.03%; N 6.94%; Cl 18.27%.

~3 , -- ~ _

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for preparing racemic or optically active compounds of the formula I

(I) and pharmaceutically acceptable salts thereof (wherein R1 and R2 are hydrogen or lower alkyl of 1 to 4 carbon atoms and R3 is halogeno-alkenyl of 2 or 3 carbon atoms, the halogen being chlorine or bromine, or propynyl), which comprises a) reacting a compound of the formula II

(II) with a compound of the formula III
B - R3 (III) (wherein R1, R2, R3 are as defined above, and A and B stand for groups, which on reaction between the compound of formula II and formula III form a bi-valent group of the formula R2 -? or comprise the said bivalent radical) and, if required, converting a halogeno-alkenyl group in the product obtained into a propynyl group; or b) reacting a compound of the formula (VI) with a compound of the formula V
(V) with simultaneous or subsequent reduction; or c) condensing a compound of the formula IV

(IV) with formaldehyde and acetylene and, if required, converting a product of formula I obtained into a pharmaceutically acceptable acid addition salt or setting free a product of formula I from its acid addition salt and, if required, separating a racemic compound of the formula I into its optically active isomers.

2. A process according to claim 1 wherein method (a) is used and a compound of the formula II in which A is a group of formula -NHR2 is reacted with a compound of the formula III in which R3 is propargyl and B is halogen or a sulfonic acid ester group.

3. A process according to claim 2 wherein B is an alkylsulfonyloxy or arylsulfonyloxy group.

4. A process according to claim 2, wherein in the starting material of formula III B is chlorine, bromine, methane sulfonyl or p-toluene sulfonyloxy.

5. A process according to claim 1 wherein method (a) is used and a compound of the formula II in which A is a group of formula -NHR2 is reacted with a 1,2-dihalogeno-alkene of 2 or 3 carbon atoms, the halogen being chlorine or bromine and, if required, splitting off hydrogen halide from the halogeno-alkenyl derivative thus obtained.

6. A process according to claim 1 wherein method (a) is used and a compound of the formula II in which A is a group of formula -NHR2 is reacted with propargyl aldehyde, with simultaneous or subsequent reduction.

7. A process according to claim 1 wherein method (a) is used which comprises reacting a compound of the formula VII

(VII) with a compound of formula V

(V) (wherein R1, R2 and R3 are as defined in claim 1, and X stands for halogen or a sulfonic acid ester group).

8. A process according to claim 7 wherein X stands for an alkylsulfonyl-oxy or arylsulfonyloxy group.

9. A process according to claim 7, which comprises reacting a 2-furyl-ethyl halide with methyl-propynyl amine.

10. A process according to claim 1 wherein R3 is a bromopropenyl group.

11. A process according to claim 1 wherein R1 and R2 are both methyl groups and R3 is a propynyl group.

12, A process according to claim 1 wherein R1 is hydrogen, R2 is a methyl group and R3 is a propynyl group.

13. Compounds of formula I as defined in claim 1 and pharmaceutically acceptable salts thereof when prepared by a process according to claim 1 or an obvious chemical equivalent thereof.

14. A process for preparing N-methyl-N-[1-methyl-2-(furyl-2) -ethyl-propynylamine which comprises refluxing N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-amine with propargyl bromide in toluene and in the presence of sodium hydroxide.

15. A process for preparing N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine which comprises reacting N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-amine with 1,2-dibromo-propene to obtain N-methyl-N-[1-methyl-(furyl-2)-ethyl]-N-2-bromopropenylamine and dehydrobrominating this compound by reaction with potassium hydroxide.

16. A process for preparing N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine which comprises reacting 2-furyl-acetone with methyl-propynylamine in the presence of nascent hydrogen.

17. A process for preparing N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine which comprises reacting N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-amine with propargyl aldehyde in the presence of nascent hydrogen.

18. A process for preparing N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine which comprises reacting N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-amine with acetylene and paraformaldehyde in solution in dioxane.

19. The compound N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine when prepared by a process according to claim 14, 15 or 16 or an obvious chemical equivalent thereof.

20. The compound N-methyl-N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine when prepared by a process according to claim 17 or 18 or an obvious chemical equivalent thereof.

21. A process for preparing N-methyl-N-[2-(furyl-2)-ethyl]-propynylamine or its hydrochloride salt which comprises refluxing N-methyl-N-[2-(furyl-2)-ethyl]-propynylamine with propargyl bromide in toluene and in the presence of sodium hydroxide and, if required, reacting the product with hydrogen chloride to obtain the hydrochloride salt.

22. A process for preparing N-methyl-N-[2-(furyl-2)-ethyl]-propynylamine or its hydrochloride salt which comprises reacting N-methyl-N-2-(furyl-2)ethylamine with 1,2-dibromopropene to obtain N-methyl-N-[2-(furyl-2)-ethyl]-2-bromo-propenylamine, dehydrobrominating this compound by reaction with potassium hydroxide and, if required, reacting the product with hydrogen chloride to obtain the hydrochloride salt.

23. The compound N-methyl-N-[2-(furyl-2)-ethyl]-propynylamine or its hydrochloride salt when prepared by a process according to claim 21 or 22 or an obvious chemical equivalent thereof.

CLAIMS SUPPORTED BY SUPPLEMENTARY DISCLOSURE:

24. A process for preparing N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine or its hydrochloride salt which comprises reacting 1-methyl-2-(furyl-2)-ethylamine with acetylene paraformaldehyde in solution in dioxane.

25. The compound N-[1-methyl-2-(furyl-2)-ethyl]-propynylamine or its hydrochloride salt when prepared by a process according to claim 24 or an obvious chemical equivalent thereof.