CS216172B2 - Method of making the n-substituted n-2-+l2-furylethyl+p-amines - Google Patents

Description

The present invention relates to a process for the preparation of N-substituted N-2- (2-furylethyl) amines of the general formula I (II).

wherein each of R ¹ and R ² is hydrogen or C 1 -C 4 alkyl and

R ³ represents a propynyl group and salts thereof.

According to the invention, the compounds of the formula I as well as their salts are prepared by the preparation of 2-furylacetone of the formula II, wherein:

R ¹ has the abovementioned meanings, is reacted with an amine of formula III

HN — R ³

AND

R ² (III) wherein

R ² and R ³ are as defined above, and the product during or after the reaction is reduced, whereupon the obtained compound of formula I optionally converted in its salt or from its salt is released.

The condensation is carried out by mixing the reactants, optionally in the presence of a solvent. For the reduction, which is carried out during or after the reaction, preferably hydrogen is used in the form of birth.

The compounds produced by the process of the invention may be reacted with biologically preferred or indifferent acids to form salts thereof, or may be liberated from their salts when purification of the compounds is accomplished by conversion to salts. Inorganic acids such as hydrochloric acid, sulfuric acid or phosphoric acid and organic acids such as maleic acid, lactic acid, citric acid, ascorbic acid, etc. are suitable for salt formation.

Compounds of formula I in which R ¹ represents an alkyl group containing chirólní carbon atom and is optically active. Optically active isomers can be obtained when racemic compounds of formula I are resolved into their optically active antipodes, or when starting from optically active compounds of formula II.

The compounds of formula I are novel. Their pharmacological activity is similar to that of phenylethylamine [J. Pharmacol. 72, page 265 (IS11) j. However, the N-substituted 2- (2-furylethyl) -amines of formula I produced by the process of the invention do not have an undesired amphetamine effect but surprisingly selectively inhibit the monoamine oxidase. of the invention [Biochemical Pharmacology, 18, 1447 (1969); Brit. J. Pharmacology, 45, 490 (1972)]. However, the compounds described therein mainly inhibit the oxidation of 5-hydroxytryptamine, only Na-dimethyl-N -. phenylethyl-N-propynylamine, described in earlier British Patent No. 1,031,225, has a similar inhibitory effect on benzylamine oxidation [Brit. J. Pharmacology, 45, p. 490 (1972)]. pharmacological effects.

Benzylamine oxidation in the liver is inhibited, for example, by N-methyl-N-propynyl-N- (2-furylethyl) amine in vivo at a dose of 6.25 mg / kg of 79%, while at the same dose the inhibition of tyramine oxidation is only 44% . N-methyl-N-propynyl-N- (2-furyl-1-methylethyl) -amine inhibits 53% oxidation of benzylamine in the brain at 5 mg / kg, 5% hydroxytryptamine oxidation by only 2% / o. At the same dose, 1-N-methyl-N-propynyl-N- (2-phenyl-1-methylethyl) -amine shows an inhibition of benzylamine oxidation by 80% in the brain, and an inhibition of 5-hydroxytryptamine oxidation of 15% / ο. At a dose of 10 mg / kg, the phenyl derivative inhibits the oxidation of benzylamine in the liver by 78%, the oxidation of 5-hydroxytryptamine by 56%.

These data indicate that furan derivatives have a more selective effect than known phenyl derivatives in inhibiting monoamine oxididase. Even more pronounced is the selectivity in in vitro experiments. Even the antidepressant effect of furan derivatives, the antagonist effect of reserpine, is greater than that of similar phenyl compounds. Furan derivatives are less toxic than the corresponding phenyl derivatives.

The compounds produced by the process according to the invention or their salts can be formulated in a known manner into medicaments. For the manufacture of medicinal preparations, the compounds produced by the process according to the invention are mixed, for example, with liquid or solid fillers, carriers and auxiliaries such as glidants, flavoring agents, preservatives, etc., and formulated in known manner into ready-to-use medicaments in the form of tablets, dragees, capsules, microcapsules, suppositories, powder mixtures, aqueous suspensions, solutions, etc. The medicinal preparations are preferably administered orally and aprenterally.

The method according to the invention is illustrated in more detail by the following example:

To a solution of 12.4 g (0.1 mol) of 2-furylacetone in 100 ml of alcohol is added 7.25 g (0.105 mol) of methylpropinylamine. 3.5 g of aluminum foil are degreased with alcohol and 1 g of mercuric chloride and 15 g of sodium chloride in 30 ml of water are activated. After 6-8 minutes, the activation solution is decanted, the activated aluminum foil is washed with cold water and added to the above solution with stirring. The temperature is maintained between 15 and 30 ° C by cooling. After stirring for 24 hours, 30 ml of 40% sodium hydroxide solution was added. The phases were separated, and the aqueous phase was extracted three times with benzene. The benzene extracts were combined with the alcohol phase obtained during phase separation, and the resulting mixture was then concentrated. The remaining oil is an oily organic phase and an aqueous phase. The aqueous phase is extracted with benzene, the benzene solution is dried over potassium carbonate, the benzene is distilled off and the residue is distilled off under reduced pressure. 6.7 g of N-methyl-N- [1-methyl-2- (2-furyl) -ethyl] -propinylamine are obtained, boiling in the range of 113-115 [deg.] C. at a pressure of 2.67 kPa; n _D ²⁰ - 1.4905.

Claims (1)

SUBJECT A method for producing N-substituted N-2- (2-furylethyl) amines of Formula I (^ -CH = CH-NR ³ (Ij wherein each of R ¹ and R ² represents hydrogen or alkyl with 1 to 4 carbon atoms and R ³ represents a propynyl group and salts thereof, characterized in that the 2-furylacetone of the general formula II: R ¹ has the abovementioned meanings, is reacted with an amine of formula III HN — R ³ R2 (III) wherein R ² and R ³ are as defined above, and the product during or after the reaction is reduced and the resulting compound of formula I is optionally converted into its salt is released from their salts. II-CH, rCO (II)