CH639080A5 - Process for the preparation of a 3-substituted-tetrahydro-1,2,4-triazine - Google Patents

Description

The subject of the present invention is a general process for the preparation of tetrahydro-1,2,4-triazines-3-substituted, the new compounds prepared by the process according to the invention and the pharmaceutical compositions comprising these compounds. In accordance with the present invention, the process for preparing tetrahydro-1,2,4-triazines-3-substituted comprises reacting a nitrile with a 2-aminoethylhydrazine or a substituted 2-aminoethylhydrazine in the presence of an amount catalytic of a salt of a transition metal or elemental sulfur. The new compounds obtained according to the present process are the tetrahydrotriazines of general formula:

^ N-fL

I

n r-

ch / \

<C, l2> n a

<ciyra

B

55 in which m and n, independently, equal 0 or 1, R is a hydrogen atom, a methyl or acetyl group, R! is a hydrogen atom or a methyl group, A and B independently represent a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, naphthyl, 1,3-benzodioxol-5-yl, phenyl, 60 phenyl -substituted. The phenyl ring substitutions described above can include almost any group which does not react with hydrazine under the conditions of the reaction process. Such substitutions include the following: halogenol, lower alkyl, lower alkoxy, nitro, naphthyl and pyridyl. 65 As used herein, the term alkyl and lower alkoxy refers to a group having 1 to 3 carbon atoms.

The present tetrahydrotriazine-3-substituted are 3- (1,2-diarylethyl) -1,4,5,6-tetrahydro-1,2,4-triazines substituted for-

639,080

4

mule I in which m = 0, n = 1, R is a hydrogen atom, a methyl or acetyl group, R] is a hydrogen atom or a methyl group, A and B independently represent a naphthyl group, l, 3-benzodioxol-5-yl, phenyl or phenyl substituted by one or two fragments chosen from the following: lower alkyl, lower alkoxy, halogen and naphthyl, provided that A is not a phenyl group when B is a phenyl or naphthyl group . The present compounds have been found to have both antidepressant and anti-anxiety activity when administered internally to a mammal. The term psychoactive agent used in the description and the claims relates to a compound having both anti-anxiety and anti-depressant properties.

A subject of the invention is also the pharmaceutically acceptable salts of the present 3- (1,2-diarylethyl) -1,4,5,6-tetrahydro-1,2,4-triazines; the expression pharmaceutically acceptable salts used in the description and the claims relates to non-toxic acid addition salts of compounds whose anions are relatively harmless to animals in doses consistent with good psychoactive activity, so that the beneficial effects of the free base are not spoiled by the side effects that could be attributed to anions. Pharmaceutically acceptable salts including those derived from mineral acids such as hydrochloric and sulfuric acid and organic acids such as lactic, maleic, succinic, fumaric, glutaric, citric, malic, p-toluenesulfonic, methanesulfonic, tartaric,

etc.

A preferred group of the present compounds includes those of formula I in which m = 0, n = 1, R and Rt are a hydrogen atom, one of A and B represents a phenyl-substituted group and the other represents a phenyl or phenyl-substituted group where the substitutions on the phenyl rings are chosen from the following: lower alkyl, lower alkoxy and halo, and their pharmaceutically acceptable salts.

Various substituted 1,4,5,6-tetrahydro-1,2,4-triazines are described as having antidepressant properties in US Patent No. 3,471,486.

3- (1,2-diphenylethyl) -1,4,5,6-tetrahydro-1,2,4-tri-azine has been described as an antidepressant agent in "Journal of Medicinal Chemistry", 12.257 (1969) . This compound was tested for anti-anxiety activity and found to be practically inactive. In general, the compounds are prepared by reacting an imino ester of hydrohalic acid dissolved in glacial acetic acid, methanol or ethanol with a 2-aminoalkylhydrazine. This process for preparing the compounds is tedious and gives poor yields, making the overall process uneconomical for commercial production.

2-imidazolines substituted by the cyclization of a diamine with a nitrile have also been synthesized in the presence of elemental sulfur [“Nippon Kagaku Zasshi”, 1968, 89 (8), 780; "Chem. Abs. ”, 70: 19983q].

The present process for preparing tetrahydro-1,2,4-triazine-3-substituted can be represented as follows:

r ri hn-ch2-ch2-n-nh2

1

B "(cVm

A- (CH2) n sulfur or salt of a transition metal ch-cn

where m, n, R, R], A and B are as defined above.

The reaction of nitrile with 2-aminoethyl hydrazine can be carried out in a suitable solvent system, usually a high boiling alcohol, but the reaction can also be carried out in the absence of a solvent simply by mixing together bodies reacting with a catalytic amount of a salt of a transition metal or elemental sulfur. Generally the reaction continues more quickly in the absence of solvent but, when preparing the product in large batches, it is often advantageous to use solvent to lower the viscosity of the reactants to facilitate mixing. As used herein, the term catalytic amount refers to the amount of transition metal salt or elemental sulfur required to convert equimolar amounts of hydrazine and nitrile to 1,2,4-triazine which is the product.

It is found that, among the transition metal salts, ferric chloride and zinc acetate have given satisfactory results. Elemental sulfur is particularly preferred because it is easy-

n-r i 1

r-n. not

T

ch / \

(CHA

m b

50: -

ment available, that it emerges from the reaction mass and that only traces remain in the final product.

As indicated above, it has been found that sulfur is the preferred catalyst for carrying out the present process. The reaction is generally carried out at a temperature of 70-100 ° C. and preferably 85-95 ° C. It is possible to use lower temperatures, but the reaction rate is slowed down. Temperatures above about 120 ° C cause the hydrazine / sulfur complex to vaporize out of the reaction mixture and lead to cloudy yields and the formation of impurities.

The various intermediate nitriles are prepared by known methods described in the literature. See for example “Synthesis”, 441-456, August 1973: “J. Org. Chem. ”, 36, 2948 (1971) and“ Tetra-65 hedron Letters ”, N ° 14, pp. 1509-1511 (1966). The 2-aminoethylhydrazines are also prepared according to the methods of the literature.

Tetrahydrotriazines which are the products obtained by the reaction described above can easily be converted into their halogen-

5

639,080

hydrate if desired, by acidification with a hydrohalic acid that previously chosen.

One can also easily obtain compounds of formula I in which R! is a methyl group and R is a hydrogen atom, a methyl or acetyl group, from the corresponding N-non-substituted compounds by common methods of methylation or acetylation.

For the implementation of the invention, the production of 3- (1,2-diphenylethyl) -1,4,5,6-tetrahydro-1,2,4-triazine was carried out in experimental development studies at both in laboratory scale and large scale production batches, as described below.

The most convenient is to prepare 3- (1,2-diphenylethyl) -1,4,5,6-tetrahydro-1,2,4-triazine by a two-step synthesis, and the second step is the process which is the object of the present invention. In the first step, 2,3-diphenylpropionitrile is produced by a catalytic phase transfer reaction involving benzyl cyanide and benzyl chloride in the presence of aqueous sodium hydroxide. Reactions of this general type are well documented in the literature. In the second step, the 2,3-diphenylpropionitrile and the 2-aminoethylhydrazine are cyclized in the presence of sulfur to obtain 3- (1,2-diphenylethyl) -1,4,5,6-tetrahydro-1,2, 4-triazine. The triazine can easily be converted into the hydrochloride if desired, by acidification with a halogenohydrous acid chosen beforehand.

As indicated above, the present substituted 3-diarylethyltetrahydro-1,2,4-triazines having anti-anxiety activity are readily prepared by the method disclosed above.

The anti-anxiety and antidepressant properties of the present substituted 3-diarylethyltetrahydrotriazines have been proven by pharmacological experiments.

Compounds which have anti-anxiety properties block the elevation of corticosteroid levels in stress-induced serum. See “British Medicai Journal”, 1971 (2), pp. 310-313. The corticosteroid levels of stressed male rats previously treated with 20 mg / kg of the active compound administered by intraperitoneal injection were compared to the corticosteroid levels of stressed male rats previously treated with saline. 3 ml of blood were collected by cardiac puncture after methoxyfluran anesthesia. After coagulation, the blood was centrifuged to separate the serum for use in corticosteroid analysis.

The analysis was performed by adding 5 ml of methylene chloride to 300 µl of the serum sample, then swirling the sample for 15-20 s. The samples were then centrifuged at 41 x g for about 5 min. The lipid layer was removed by suction and 3 ml of the methylene chloride fraction was transferred to a clean tube. To this sample was added 3 ml of fluorescence reagent (25% ethanol and 75% concentrated sulfuric acid) and it was vortexed for 5 s. The fluorescence development was complete after 20 min and was measured using a Perkin-Elmer® fluorometer Model 204 device at an excitation wavelength of 470 m | i and a wavelength of the 530 mp analyzer. This assay measures free cortisol and corticosterone. Corticosteroid values were calculated as follows:

corticosteroid (| xg%) =

fluorescence of the sample - fluorescence of the blank test x 25 | ig%

fluorescence of the standard - fluorescence of the blank test

By proceeding as described above, it has been shown that the present compounds have anti-anxiety activity. The results are shown in Table II. Values below 100% indicate activity.

The antidepressant effect has been proven by the reserpine ptosis test. Groups of four mice were administered 30 mg / kg of 3- (1,2-diarylethyl) -1,4,5,6-tetrahydro-1,2,4-triazine by intraperitoneal injection with an aqueous vehicle. To a group of analogous mice which served as a control, only the vehicle was injected. After 30 min, the two groups of mice were injected subcutaneously with 2.5 mg / kg of reserpine. It results from the administration of reserpine to the control mice a classic progression of the symptoms which begin with a drooping of the eyelids (ptosis) and which later culminate in a generalized depression with a decreased spontaneous motor activity and a reduced response to stimuli. auditory and tactile. The animals to which triazine was injected received scores after 45 min on the following basis: no ptosis = 0, partial ptosis = 1, complete ptosis = 2. Complete protection against ptosis induced by reserpine gives a value of 0 or 100%. The percentage of protection for each compound is indicated in Table I.

Table I

Composed of example N °

% inhibition of ptosis induced by reserpine

Corticosteroid level in serum 0 * g%)

13

63

25

14

88

13

15

38

82

16

38

67

17

25

32

18

50

62

19

88

75

20

38

52

21

50

33

22

25

33

23

88

39

24

63

79

25

13

72

26

42

39

27

25

62

28

50

77

29

13

77

control (saline solution)

0

100

It can be seen from Table I that the compounds of Examples 13, 14, 21, 22 and 26 are particularly active as anti-anxiety agents. The other compounds indicated in the table, while generally being less active than the compounds of Examples 13, 14, 21, 22 and 26, also exhibit significant activity as an anti-anxiety agent. In addition to the anti-anxiety properties already indicated, it has been found that the following compounds are also very active as antidepressant agents and that they are particularly preferred, therefore, as psychoactive agents, that is to say agents having both anti-anxiety and antidepressant properties:

3- [2- (4-chlorophenyl) -1 -phenylethyl] monohydrochloride -1,4,5,6-

tetrahydro-1,2,4-triazine (Example 14);

3- [1- (4-methylphenyl) -2-phenylethyl] -1,4,5,6- monohydrochloride

tetrahydro-1,2,4-triazine (Example 16);

3- [2- (2,6-dichlorophenyl) -1-phenylethyl] -1,4,5,6-tetrahydro-1,2,4-triazine monohydrochloride (Example 23). "

For the treatment of anxiety, one or more of the present compounds is administered internally to a mammal by an effective route to introduce an effective anti-anxiety amount of the compound into the blood system of the mammal. Administration may be carried out parenterally, for example by intravenous, intraperitoneal, subcutaneous or intramuscular injection or by introduction into the gastrointestinal tract by the oral route, for example introduction of the compound into the blood by the gastrointestinal tract. Compounds are effective orally and generally have a higher toxic dose / effective dose ratio

5

10

15

20

25

30

35

40

45

50

55

60

65

639,080

6

when administered orally, and this is the preferred route of administration.

Generally, the active compounds are administered at a dose of about 0.2 to 40 mg / kg of body weight and preferably about 0.5 to 5 mg / kg of body weight. Higher doses may be used, for example when the compound is administered orally in a dose form which is gradually released (times release dosage). In the case of mammals suffering from anxiety of the central nervous system, that is to say which exhibit symptoms of anxiety, preferably an anti-anxiety amount of the compound is administered several times at predetermined intervals.

In general, it is advantageous to administer the individual doses at the lowest anti-anxiety amount which produces the desired continuity which corresponds to a convenient dose administration schedule.

Preferably, the active ingredient is incorporated into a composition comprising a pharmaceutical vehicle and from approximately 0.001 to 95% by weight of the compound. The term pharmaceutical vehicle refers to pharmaceutical excipients useful for the preparation of pharmacologically active compositions for internal administration to animals and which are practically non-toxic and non-sensitizing under the conditions of use.

Suitable pharmaceutical vehicles are known and disclosed in publications such as: "Remington's Pharmaceutical Sciences", 13th ed., Martine (ed.) Mack Publishing Co., Easton, Pa. (1965). The compositions can be prepared by known techniques for the preparation of tablets, capsules, lozenges, trochisques, elixirs, syrups, emulsions, dispersions, wettable and effervescent powders, sterile injectable compositions, and they may contain suitable excipients known to be useful for the preparation of the type of composition desired.

Dose units suitable for oral administration such as tablets, capsules, lozenges, elixirs, syrups, etc. are preferred and the active compound can be made up into release time capsule compositions controlled or tablet. "

Preferred compositions include sterile injectable solutions containing about 0.001 to 10% by weight of the compound in a pharmaceutical vehicle suitable for injection, for example isotone saline, Ringer's injection USP and Ringer's milk USP , etc.

The following examples illustrate the invention.

Example 1:

Preparation of 3- (1,2-diphenylethyl) -l, 4,5,6- hydrochloride

tetrahydro-1,2,4-triazine

Step 1 :

Is introduced into a flask of 21 fitted with a mechanical stirrer, a thermometer, a nitrogen inlet and a reflux condenser 585 g (574 ml; 5.0 mol) of benzyl cyanide, 250 ml 50% sodium hydroxide and 12.5 g (0.055 mol; 4.4 mol%) of benzyltriethylammonium chloride. While maintaining the temperature at about 50 ° C in a cold water bath, 224.4 g (1.77 mol) of benzyl chloride is added slowly dropwise over about 1 h. The reaction mass is stirred for another 1 h, then 400 ml of deionized water are added to dissolve the sodium chloride and cause separation of the aqueous and organic layers. During this step, if an emulsion is formed, methylene chloride is added. The organic layer is distilled to separate the 2,3-diphenylpropionitrile from other reactants and impurities. The identity of the compound was confirmed by elemental analysis, NMR, IR, and mass spectrometry.

2nd step:

The nitrile which is the intermediate compound of stage 1 (35.0 g; 0.169 mol) is heated under nitrogen with 0.379 g (0.012 gram-atom, 7 mol%) of sulfur to approximately 70 ° C. in a balloon

100 ml round bottom until sulfur dissolves (approximately 2 h). The reaction vessel is charged with 25.4 g (0.338 mol; 2 Eq) of 2-aminoethylhydrazine. The temperature is increased to about 100 ° C and maintained at this temperature for about 5 h.

The reaction mass is cooled to approximately 50 ° C., then 75 ml of toluene are added, then extraction is carried out with 75 ml of water. 35 ml of absolute alcohol are added and the mixture is heated to reflux while bubbling HCl into the flask.

3- (1,2-diphenylethyl) -1,4,5,6-tetra-hydro-1,2,4-triazine monohydrochloride separated by crystallization and was separated by filtration, then washed with a 90/10 mixture of toluene / ethanol. The product is dried under vacuum. Elemental analysis, X-ray crystallography, NMR, and mass spectrophotometry were used to confirm the structure.

Using the process outlined above, a number of related compounds of the formula were prepared:

In which k = 1 or 2. These compounds are indicated in Table II:

Table II

35

40

45

Compound No

R

R '

R "

2

CH3

H

H

3

H

H

4-OCH3

4

H

4-N02

H

5

H

3,4-diOCH3

H

6

H

2-pyridyle

H

7

H

4-pyridyle

H

8

H

2-naphthyle

2-naphthyle

9

H

H

2-naphthyle

10

H

H

1-naphthyle

11

H

1-naphthyle

H

In addition to the compounds from the above list, compounds which do not correspond to the general formula in Table II n / a have been prepared using the present method. These compounds include the following:

1,4,5,6-tetrahydro-3- (2-naphthalenyl-) monohydrochloride

methyl) -1,2,4-triazine, and 3- {2- (4-chlorophenyl) -1 - [(4-methylphenyl) sulfonyl] ethyl} -55 l, 4,5,6-tetrahydro-1, 2,4-triazine.

Example 12

Using practically the methods outlined above, two batches were prepared containing 25.5 and 26.5 kg of 60 3- (1,2-diphenylethyl) -1,4,5,6-tetrahydro-1,2 hydrochloride. , 4-triazine. The crude yield was found to be 65.1 and 70.0%, respectively. After recrystallization from ethanol, the yield of purified product was 42.5 and 53.1% respectively.

It has been found that the sulfur which is the catalyst can be added directly to the molten nitrile without the long heating required to dissolve the sulfur in step 2 of the reaction. Thus, the overall time for the batch was significantly reduced compared to that of Example 1 above.

7

639,080

Example 13:

Preparation of 3- [2- (4-fluorophenyl) -1- (phenylethyl) Jl, 4,5,6-tetrahydro-1,2,4-triazine hydrochloride A mixture containing 5.0 g of l- phenyl-2-p-fluorophenylpropionitrile and 0.5 g of elemental sulfur in a 50 ml round bottom flask fitted with a condenser, a magnetic stirrer and kept under a nitrogen atmosphere. A minimum amount of 2-methoxyethanol (5 ml) was added and the mixture was heated at 90 ° C for 2 h to dissolve the sulfur. 3.3 g of 2-aminoethyl hydrazine was slowly injected into the heated solution. and the blue-green reaction mass was heated at 90 ° C for 18 h.

The reaction mass was quenched by adding 30 ml of toluene, transferred to a separatory funnel, then another 70 ml of toluene was added.

The toluene was washed with water and with a saturated sodium chloride solution. The organic layer was separated, dried with sodium sulfate and filtered. Dry HCl gas was bubbled through the toluene solution to obtain 3- [2- (4-fluorophenyl) -1 - (phenylethyl)] - 1,4,5,6-tetrahydro-1,2,4 monohydrochloride -triazine in the form of a precipitate. The crude product was dried in vacuo and recrystallized from isopropanol. The salt was found to melt at 200-222 ° C.

Elemental analysis indicated 63.95% carbon, 6.02% hydrogen and 13.09% nitrogen, compared to theoretical values of carbon = 63.84%, hydrogen = 5.79% and nitrogen = 13.14%.

Proceeding practically as described in Example 13 above, several other 3- (1,2-diarylethyl) -1,4,5,6-tetrahydro-1,2,4-triazines of the formula were prepared. general:

at

The compounds are described in Table III.

In addition to the compounds shown in Table III, two compounds bearing substituents on the triazine ring were prepared. It was:

Example 28: 3- [2- (4-chlorophenyl) -1-phenylethyl] -1,4,5,6-tetrahydro-1-methyl-1,2,4-triazine hydrochloride.

Example 29: 4-acetyl-3- (1,2-diphenyl-ethyl) -1,4,5,6-tetrahydro-1-methyl-1,2,4-triazine hydrochloride.

40

5

Table III

Ex.

AT

B

P.F.

No

AT

(° C)

14

p-chlorophenyl phenyl

212-213

15

-fluorophenyl p-methoxyphenyl

145-147

16

phenyl p-methylphenyl

217-219

17

m-methylphenyl phenyl

184-186

18

p-methylphenyl phenyl

141-143

19

m-chlorophenyl phenyl

144-146

20

phenyl m-methylphenyl

177-178.5

21

phenyl

1,3-benzodioxol-5-yl

95-98

22

3,4-dimethylphenyl phenyl

211-213

23

2,6-dichlorophenyl phenyl

135-138

24

3,4-dichloropheny phenyl

224-225

25

1-naphthyl phenyl

248-249

26

2-naphthyl phenyl

219-220

27

m-fluorophenyl phenyl

233-235

R

Claims (25)

639,080 2 claims 1. Process for the preparation of a substituted tetrahydro-l, 2,4-triazine-3, characterized in that a nitrile is reacted with 2-aminoethylhydrazine or a substituted 2-aminoethylhydrazine in the presence of a catalytic amount a transition metal salt or elemental sulfur. 2. Method according to claim 1, characterized in that the 2-aminoethylhydrazine has the following formula: r rj I I hn - ch2 - ch2 - n - nh2 and in that the nitrile has the following formula: a— (ch2) n. \: h-cn b- (ch2) m / in which m and n, independently, are 0 or 1, R is a hydrogen atom or a methyl group, Rj is a hydrogen atom or a methyl group and A and B independently represent a hydrogen atom, a group alkyl having from 1 to 4 carbon atoms, naphthyl, 1,3-benzodioxol-5-yl, phenyl, phenyl-substituted, said substitutions on the phenyl ring being chosen from the following: halo, lower alkyl, lower alkoxy, nitro, naphthyle and pyridyle. 3. Method according to claim 2, characterized in that the 2-aminoethylhydrazine is represented by the formula: R Rt I I hn-ch2-ch2-n-nh2 and the nitrile is represented by the formula: a— (ch2) n> \: h-cn b- (ch2) „/ in which m and n, independently, are 0 or 1, R is a hydrogen atom or a methyl group, Rt is a hydrogen atom, A and B independently represent a hydrogen atom, an alkyl group having 1 with 4 carbon atoms, phenyl, phenyl-substituted, these substituents on the phenyl nucleus being chosen from the following: halo, lower alkyl, lower alkoxy, nitro, naphthyl and pyridyl. 4. Method according to claim 2, characterized in that R is a hydrogen atom, or a methyl group, Rj is a hydrogen atom or a methyl group, m = 0, n = 1 and A and B independently represent a naphthyl, 1,3-benzodioxol-5-yl, phenyl or phenyl group substituted by one or two fragments chosen from the following: lower alkyl, lower alkoxy, halogen and naphthyl, provided that A is not a phenyl group when B is a phenyl or naphthyl group. 5. Method according to claim 3, characterized in that R and Rt are a hydrogen atom, m = 0, n = 1 and A is a phenyl or phenyl-substituted group and B is a phenyl or phenyl-substituted group. 6. Method according to claim 4, characterized in that R and R! are a hydrogen atom, one of A and B represents a phenyl-substituted group and the other represents a phenyl or phenyl-substituted group where the substitutions on the phenyl ring are chosen from the following: lower alkyl, lower alkoxy and halo. 7. Method according to claim 5, characterized in that the nitrile, which is 2,3-diphenylpropionitrile, is reacted with 2-aminoethylhydrazine. 8. Method according to claim 7, characterized in that cyclizes 2,3-diphenylpropionitrile with 2-aminoethylhydrazine in the presence of a catalytic amount of elemental sulfur to obtain 3- (1,2-diphenylethyl) -l , 4,5,6-tetrahydro-1,2,4-triazine. 9. Method according to one of claims 4 to 8, further characterized in that acidifies the tetrahydro-l, 2,4-triazines-3-substituted obtained with a pharmaceutically acceptable acid to obtain one of their pharmaceutically acceptable salts . 10. The method of claim 8, further characterized in that the 3- (1,2-diphenylethyl) -1,4,5,6-tetrahydro-1,2,4-tri-azine obtained is acidified with a hydrohalic acid to obtain one of these hydrochlorides. 11. Method according to one of claims 1 to 10, characterized in that the reaction between the 2-aminoethylhydrazine and the nitrile is carried out at a temperature between 70 and 100 ° C. 12. Process for the preparation of a new anti-anxiety compound of formula I: fTR ' "■ y /vs\ A B in which R is a methyl group, Rx is a methyl group, A and B independently represent a naphthyl, 1,3-benzo-dioxol-5-yl, phenyl or phenyl group substituted by one or two substituents chosen from the following: alkyl lower, lower alkoxy, halogeno and naphthyl, provided that A is not a phenyl group when B is a phenyl or naphthyl group, and of its pharmaceutically acceptable salts, characterized in that a 2-aminoethylhydrazine of formula is reacted: R Rt I I HN - CH2 - CH2 - N-NH2 and a nitrile of formula: A-CH2v ^^ CH-CN B in which R is a hydrogen atom or a methyl group, Rt is a hydrogen atom or a methyl group, A and B are as indicated above, in the presence of a catalytic amount of a salt of a metal of transition or elemental sulfur, a compound of formula I is obtained in which R is a hydrogen atom and Rj is a hydrogen atom or a methyl group and the said compound is converted into the corresponding compound of formula I, formula in which R is a methyl group and R! is a methyl group by methylation and, if desired, the product is converted to a pharmaceutically acceptable salt. 13. Process for the preparation of a new anti-anxiety compound of formula I: /VS\ 2 \ A B 5 10 15 20 25 30 35 40 45 50 55 60 65 3 639,080 in which R is an acetyl group, R, is a methyl group, A and B independently represent a naphthyl, 1,3-benzo-dioxol-5-yl, phenyl or phenyl group substituted by one or two substituents chosen from the following: lower alkyl, lower alkoxy, halogeno and naphthyl, provided that A is not a phenyl group when B is a phenyl or naphthyl group, and pharmaceutically acceptable salts of this compound, characterized in that a 2-aminoethylhydrazine is reacted of formula: R R, I I hn-ch2-ch2-n-nh2 and a nitrile of formula: A-CH ch-cn in which R is a hydrogen atom or a methyl group, R] is a hydrogen atom or a methyl group, A and B are as indicated above, in the presence of a catalytic amount of a salt of a transition metal or elemental sulfur, a compound of formula I is obtained in which R is a hydrogen atom and R! is a hydrogen atom or a methyl group and the said compound is converted into the corresponding compound of formula I, formula in which R is an acetyl group and Rj is a methyl group by acetylation and, where appropriate, methylation and, if desired , the product is converted into a pharmaceutically acceptable salt. 14. Compound obtained according to the process according to claim 1, with anti-anxiety action and corresponding to the formula: i / CH <° y " \ "Ty. 20. Psychoactive composition with anti-anxiety action, comprising a suitable pharmaceutical vehicle and an effective psychoactive amount of a compound of claim 14. 21. Composition according to claim 20, characterized in that R and R, in the compound are a hydrogen atom. 22. Composition according to claim 20, characterized in that R and R, are a hydrogen atom, one of A and B represents a phenyl-substituted group and the other represents a phenyl or phenyl-substituted group where the substitutions on the phenyl ring are chosen from the following: lower alkyl, lower alkoxy and halo. 23. Composition according to claim 20, characterized in that the active compound is 3- [2- (4-chlorophenyl) -1-phenylethyl] -1, 4,5,6-tetrahydro-1,2,4-triazine and its pharmaceutically acceptable salts. 24. Composition according to Claim 20, characterized in that the active compound is 3- [l- (4-methylphenyl) -2-phenylethyl] -1, 4,5,6-tetrahydro-l, 2,4-triazine and its pharmaceutically acceptable salts. 25. Composition according to Claim 20, characterized in that the active compound is 3- (2,6-dichlorophenyl) -1-phenylethyl-l, 4,5,6-tetrahydro-1,2,4-triazine and its pharmaceutically acceptable salts. (I) in which m = 0, n = 1, R is a hydrogen atom, a methyl or acetyl group, Rj is a hydrogen atom or a methyl group, A and B independently represent a naphthyl group, 1,3-benzodioxol -5-yl, phenyl or phenyl substituted by one or two fragments chosen from the following: lower alkyl, lower alkoxy, halogen and naphthyl, provided that A is not a phenyl group when B is a phenyl or naphthyl group, and the pharmaceutically acceptable salts of said compound. 15. A compound according to claim 14, characterized in that R and R, are a hydrogen atom. 16. A compound according to claim 14, characterized in that R and R, are a hydrogen atom, one of A and B represents a phenyl-substituted group and the other represents a phenyl or phenyl-substituted group where the substitutions on the phenyl ring are chosen from the following: lower alkyl, lower alkoxy and halo. 17. A compound according to claim 14, which is 3- [2 (4-chlor-phenyl) -1-phenylethyl] -1,4,5,6-tetrahydro-1,2,4-triazine and its pharmaceutically salts acceptable. 18. A compound according to claim 14, which is 3- [1- (4-methyl-phenyl) -2-phenylethyl] -1,4,5,6-tetrahydro-1,2,4-triazine and its pharmaceutically salts acceptable. 19. Compound according to claim 14, which is 3- [2- (2,6-dichlorophenyl) -1 -phenylethyl] -1,4,5,6-tetrahydro-1,2,4-triazine and its pharmaceutically salts acceptable. 30