Derivatives of 1,2,4-triazolinone

 

(57) Abstract:

Usage: in the pharmaceutical industry. The essence of the invention: derivatives of 1, 2, 4-triazolylmethyl f-ly I where Q is hydrogen, (lower) allylthiourea, or the group NR1R2where R1and R2hydrogen, lower alkyl, or lower alkenyl, or R1and R2together with the nitrogen atom to which they are bound, form morpholino, piperidino or 4 methylpiperazine group, Y-C1-C4alkyl substituted by hydroxy or one or two C1-C4alkoxygroup, di (C1-C4alkoxyphenyl C1-C4alkyl or phenoxy C1-C4alkyl, substituted on the phenyl end C1-C4the alkyl containing piperidinium, or their acid-additive pharmaceutically acceptable salts, possessing anxiolytic, antidepressant, antispasmodic, anti-inflammatory, analgesic and antiperistaltic action. Reagent 1: deciever triazolyl f-ly II. Reagent 2: Amin f-ly III, where Q and Y are listed above; R4C1-C4alkyl. 5 table. The structure of the compounds f-ly I, II, III:

The invention relates to the production of new proizvodnyh of thiazolidine that are used in the headlights of the formula I

and their pharmaceutically acceptable salts accession acids, in which

Q represents hydrogen or heterocyclic radical may contain one or more1-C4alkyl substituents, or a radical of the formula SR', in which

R denotes a straight or branched alkyl radical containing 1-6 carbon atoms, or a radical of the formula NR2R3in which

R2and R3denote each hydrogen, straight or branched C1-C4alkyl group or a C2-C6alkenylphenol group

Y denotes alkyl WITH1-C4may contain one or more hydroxyl or C1-C4alkoxysubstituted, phenyl-(C1-C4alkyl), possibly containing on the phenyl ring WITH one or more1-C4alkoxygroup, or phenoxy-(C1-C4alkyl) possibly substituted on the phenyl ring WITH1-C4-alkyl containing heterocyclic radical that carries the nitrogen atom.

The invention includes all isomeric or tautomeric forms of the compounds of General formula I.

Compounds according to the invention have tranquilizers, antidepressant, antispasmodic, protivovospalitel the quality of raw materials and other pharmaceutically active derivatives.

The expression "heterocyclic group" used throughout the description, refers to a heterocyclic group with 4 to 8 parts, which can be obtained from compounds containing independently one or more nitrogen atoms and/or oxygen or a group that may be received or the same compounds with each other or with benzene. Such groups can be aromatic or saturated partially or fully. As examples for such groups are mentioned, for example, groups such as piperidyl, morpholinyl, piperazinil, furyl, imidazolyl, pyridyl, pyrimidinyl, pyrrolyl, pyrazolyl, pyridazinyl, isoxazolyl, pyrrolidinyl, pyrrolidinyl, imidazolidinyl, imidazolyl, pyrazolidine, pyrazoline, pyranyl or Delta-3-piperidine-1-yl.

The expression "alkyl group" refers to an unbranched or branched saturated aliphatic hydrocarbon groups containing 1-4 or 1-6 atmob carbon, for example, methyl, ethyl, propyl, n-butyl, n-butyl, and propyl, tert-butyl, pentyl, hexyl, etc.

The expression "alkoxy group" refers to groups simple alilovic esters containing alkyl group with1-C4for example, methoxy, ethoxy, tert.butoxy etc.

In ka is for example, vinyl, allyl, 2-methylallyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 2-pentenyl, 2-hexenyl etc.

Compounds of General formula I, in which Q denotes morpholino, di-(C1-C6-alkyl)-amino or 4-methylpiperazine and mean 3-(3-(piperidinylmethyl)-phenoxy)-propyl or 2-phenylethyl, possibly substituted by one or two1-C4alkoxygroup and their pharmaceutically acceptable salts accession acids have valuable pharmaceutical properties.

Particularly preferred representatives of the compounds of General formula I are the following derivatives: 1-(5-amino-3-(4-methylpiperazine)-1H-1,2,4-triazole-1-yl)-N-3-(3- (1-piperidinylmethyl) phenoxy)propyl-carbodiimide, 1-(5-amino-3-methylthio-1H-1,2,4-triazole-1-yl)-N-(2-(3,4-acid) ethyl/carbodiimide, 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1 - yl)-N-{-3-/3-(1-piperidinylmethyl)phenoxy/Pro - percarbonic, 1-/5-amino-3-dimethylamino-1H-1,2,4-triazole-1-yl/-N-}3-/3-(1-piperidinylmethyl )fingerstyle, and their pharmaceutically acceptable salts accession acid.

Compounds of General formula I are organic bases, with the result that they can be converted into a salt accession acid. Pharmaceutically acceptable the ski acids. As examples of pharmaceutically acceptable salts accession acid can be mentioned kaleidotrope (such as hydrochloride or hydrobromide), carbonates, sulfates, acetates, fumarate, maleate, citrates, ascorbate and tartratami.

According to the invention is a method of obtaining derivatives triazolinone General formula I and their pharmaceutically acceptable salts accession acid involves the reaction of complex deciever triazolyl General formula II,

in which has the specified value, and R4stands WITH1-C4-alkyl or phenyl-(C1-C4-alkyl), possibly substituted by a halogen atom, with an amine derivative of General formula III

Y-NH2where Y is the specified values, and if necessary, the conversion of compounds of General formula I thus obtained, its pharmaceutically acceptable salt accession acid, or the release of the Foundation of the General formula I from its salts accession acid, or the transformation of salt accession acid bases of General formula I into a different salt accession acid.

The reaction is preferably carried out in a solvent inert to the reactants. For this purpose, can preferably be used alcohols (such as e as chloroform, dichloromethane, 1,2-dichloroethane, 1,1,2-trichloroethylene, dioxane or dimethyl sulfoxide. The reaction is carried out at from 0 to 160aboutC, preferably from 20 to 120aboutC.

Compounds of General formula I obtained in the form of a Foundation, can be converted into a salt accession acid is known on its own methods. For this purpose the free base is introduced into reaction with the appropriate acid in an inert solvent.

Esters triazolyl General formula II used as starting materials are known compounds or can be obtained by analogy with the known connections, such as the description of the patent SSS N 3686301; a description of the U.S. patent N 3686301; the description of the patent GDR N 105897).

Amines of General formula III are commercial products or can be obtained as described in Houben-Weyl; Methods der Organischen Chemie, Band XI/I, Georg Thieme Verlag, Stuttgart, 1957.

Compounds according to the invention exhibit excellent biological activity and low toxicity. They have a sedative and/or antidepressant and antispasmodic effects, which are accompanied in some cases, anti-inflammatory, analiticheskii and antiperistaltic properties.

">

1. The antagonism to ptosis from tetrabenazine in mice.

Method.

The tests were carried out according to the method Hoffmeisteretal, which was applied to mice (Arzneim. Forschung 19, 846-858 (1969)). The group consisting of 10-20 mice each were processed in parallel by different doses of the tested compounds. The control group was treated only with the corresponding media. After 30 min was administered intraperitoneally injected tetrabenazine (3-isobutyl-1,10-dimethoxy-1,2,3,4,6,7-hexahydrobenzo(a)- hemolysin-2-it) with a dosage of 50 mg/kg Number of animals that have closed palpebral was determined in each group after 30, 60, 90 and 120 min, respectively.

Evaluation.

The average value of ptosis was calculated in each group, and the deviation from the mean in the control group (i.e. inhibition) expressed in percent. From the data obtained, the value of the ED50and therapeutic index was determined for the new tested compounds, as well as for amitriptyline. The results obtained are shown in table. 1.

therapeutic index of the compounds according to the invention is several times higher than the index of amitriptyline widely used in kriticheskoi practice with good results.

2. was treated with 6 mg/kg of reserpine, subcutaneously, according to Hoffmeister et al./Arzneim. Forschung 19, 846-858 (1969)). After 60 min, the compound was injected animals, whereas animals in the control group was treated with the corresponding media without active substance. Animals with Poziom were counted after 60 and 120 min after administration of the compounds to be tested. The evaluation was made according to the procedure outlined in the previous test. The results obtained are shown in table. 2.

Compounds of General formula I exceed the control connection as the ratio of the absolute dose and therapeutic index.

3. Inhibition spasms from pentetrazole.

Method.

Testing was carried out on white mice according to the modified method authors Banziger and Hane /Arch. Int. Pharmacodyn. 167, 245 (1967)/. Each group consisting of 6 mice were treated orally the test compound and a carrier without active substance, respectively. An hour later after processing dozirovku 125 mg/kg pentetrazole was administered to each animal administered intraperitoneally, and registered tonic extensor spasms of the rear limbs. The results are shown in table. 3.

From table. 3 it can be concluded that the compounds according to the invention excellent the repression spasms from nicotine and mortality.

Method.

The test was performed according to the method of the author Stone /Arch. Int. Pharmacodyn. 117, 419 (1958)/. The test compound and the carrier, respectively, were administered orally; an hour later, the animals received 1.4 mg/kg dose of nicotine intravenously, and registered spasms and mortality within hours for the treated and control groups. The results are shown in table. 4.

Therapeutic range test codeinone greater than the width of trihexyphenidyl used as a control substance.

5. The enhancement effect of the anesthesia from Hexobarbital.

Method.

Testing was carried out on white mice by the method of the author Kaergaard /Arch. Int. Pharmacodyn. 2, 170 (1967)/. Groups of six mice were used for each dose. Ispytyvaemoj compound was administered orally and hour after this treatment gave anesthetized with 40 mg/kg intravenous dose of hexobarbital. The control group received the media instead of the test compound.

Assessment.

Considered as having a positive reaction of those mice, which showed the time of anaesthesia 2.5 times longer than mice from the control group. Such modified values of the ED50was calculated. The results prepetition substance, from the point of view of the absolute dose and therapeutic index.

The pharmaceutical compositions according to the invention can be prepared are known in themselves methods by mixing the active ingredient with suitable inert solid or liquid carriers and bringing the mixture in herbal form.

The pharmaceutical compositions according to the invention may be suitable for oral (e.g. tablet, pill, pill coating, coated tablets, hard or soft gelatin capsule, solution, emulsion or suspension), parenteral (e.g., solution for injection) for rectal administration (e.g., suppositories).

As a carrier for the preparation of tablets, coated tablets, pills and capsules of hard gelatin, for example, you can use lactose, corn starch, potato starch, talc, magnesium carbonate, magnesium stearate, calcium carbonate, stearic acid or its salts, etc. as a carrier for capsules soft gelatin can be used, for example, vegetable oils, fats, waxes or high molecular weight alcohols suitable consistency. As carriers for solutions and syrups can be used to restrict, for example, water, vsokomolekulyarnyi, high molecular weight alcohols, glycerin or vegetable oil as a carrier. Suppositories can be prepared using, for example, oils, waxes, fats or high molecular weight alcohols suitable consistency.

In addition, the pharmaceutical preparations can contain excipients commonly used in pharmaceutical industry, for example wetting, sweetening, flavouring agents, salts, resulting in altered osmoticheskogo pressure, buffers, etc., the Pharmaceutical preparations can also contain other active ingredients.

Compounds of General formula I can preferably be used in the treatment orally in the form of tablets or capsules. Particularly preferred are tablets or capsules containing 250 mg of the active component.

Daily dose of the compounds of the General ormula I can vary within wide limits depending on several factors, for example, the activity of the active component, the patient's condition and age, severity of illness, etc. Oral dose is usually from 10 to 10,000 mg/day, preferably from 50 to 1000 mg/day. It must be emphasized that these values doses are only informative is subramania is provided the use of compounds of General formula I or their pharmaceutically acceptable salts for pharmaceutical compositions having especially tractibility, antidepressant and/or spasmolytic effects.

According to another SPECTA of the invention provides a method of tranquilizing, ntidepressants and/or skin treatment, which includes an introduction to the patient an effective amount of compounds of General formula I or its pharmaceutically acceptable salt.

The invention is further illustrated by the following examples of non-restrictive.

P R I m e R 1. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-{3-(1 - piperidinylmethyl)phenoxy/propyl}carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide dissolved in 5 ml of dimethyl sulfoxide and add 2,48 g (0,01 mol) 3-/3-(1-piperidinylmethyl)phenoxy/Propylamine to the solution at water cooling.

The reaction mixture was stirred at room temperautre 8 hours Then poured on water, the separated crystals are filtered and recrystallized first from acetonitrile and then from cyclohexane.

Output 2,89 (63%).

So pl. 128-130aboutC.

P R I m m e R 2. 1-/5-Amino-3-dimethylamino-1H-1,2,4-triazole-1-yl/-N-{3-/3-(1- piperidinylmethyl)phenoxy/propyl}carbothioamide.

Yield 2.83 g (68%).

So pl. 104-106aboutC.

P R I m e R 3. 1-/5-Amino-3-(4-methylpiperazine)-1H-1,2,4-triazole-1-yl)-N-{4-/3- (1-piperidinylmethyl)phenoxy/propyl}carbothioamide.

2,72 g (0,01 mol) of methyl 1-/5-amino-3-(4-methylpiperazine)1H-1,2,4-triazole-1-yl/- carbodiimide dissolved in 5 ml of dimethylsulfoxide and the solution is added 2,48 g (0,01 mol) 3-/3-(1-piperidinylmethyl) phenoxy/Propylamine cooling water. The reaction mixture was stirred at room temperature for 8 hours and Then added dropwise to 1 ml of water, the mixture is stirred for 1 h, and then added dropwise to 10 ml of n-hexane. The reaction mixture is further stirred for 1 h, separated crystals and is filtered off and recrystallized from 2-propanol.

Yield 2.83 g (68%).

So pl. 92-93aboutC.

P R I m e R 4. 1-(5-Amino-3-piperidinyl-1H-1,2,4-triazole-1-yl)-N-{3-/3-(1- piperidinylmethyl)phenoxy/propyl}carbothioamide.

to 2.57 g (0,01 mol) of methyl 1-(5-amino-3-piperidinyl-1H-1,2,4-triazole-1-yl) carbodiimide dissolved in 5 ml dimethylsulfoxide the mixture is stirred for 8 h at room temperature. Then dropwise thereto was added 1 ml of water, the mixture is stirred for 1 h, and then added dropwise to 10 ml of n-hexane. The reaction mixture is further stirred for 1 h, the separated crystals are filtered off and recrystallized from 2-propanol.

Output 3,74 g (82%).

So pl. 107-108aboutC.

P R I m e R 5. 1-/5-Amino-3-diallylamine-1H-1,2,4-triazole-1-yl/-N-{3-/3-(1- piperidinylmethyl)phenoxy/propyl}carbothioamide.

1,69 g (0,01 mol) of methyl 1-(5-amino-3-diallylamine-1H-1,2,4-triazole-1-yl) carbodiimide dissolved in 5 ml of dimethylsulfoxide and the solution is added 2,48 g (0,01 mol) 3-/3-(1-piperidinylmethyl)phenoxy/Propylamine cooling water. The reaction mixture was stirred at room temperature for 8 hours Then added dropwise 1 ml of water, the mixture is stirred for 1 h, and then added dropwise 50 ml of n-hexane. The reaction mixture is further stirred for 1 h, the separated crystals are filtered off and recrystallized from 2-propanol.

The output of 3.65 g (78%).

So pl. 94-96aboutC.

P R I m e R 6. 1-/5-Amino-3-methylthio-1H-1,2,4-triazole-1-yl-N-/2-(3,4-acid) ethyl/carbothioamide.

2.20 g (0,01 mol) of methyl 1-/5-amino-3-methylthio-1H-1,2,4-triazole-1-yl/carbolitium cooling water. The reaction mixture was stirred at room temperature for 8 hours Then poured into 15 ml of water, the separated crystals are filtered and recrystallized from ethanol.

The output of 2.44 g (69%).

So pl. 135-137aboutC.

P R I m e R 7. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N/2-(3,4 - acid) ethyl/carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl) carbodiimide dissolved in 10 ml of dimethyl - sulfoxide and to the solution add 1,81 g (0,01 mol) of 2-(3,4-acid) ethylamine by cooling water. The reaction mixture was stirred at room temperature for 8 hours Then poured into 15 ml of water allocated, the crystals are filtered and recrystallized from ethanol.

The output of 2.66 g (84%).

So pl. 142-143aboutC.

P R I m e R 8. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(3-oksipropil) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl) carbodiimide boiled in 25 ml of methanol, in the presence of 0.92 ml (0.12 moles) of 3-aminopropanol for 1 h under stirring. Then the reaction mixture is evaporated to dryness and the residue will recrystallized from acetonitrile.

Yield 2.70 g (94%).

So pl. 116-118about

Output 2,48 g (84%).

So pl. 116-118aboutC.

P R I m e R 10. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(2-oxyethyl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide boiled in 25 ml of methanol in the presence 0,72 ml (0.12 moles) of 2-aminoethanol for 1 h under stirring. Then the reaction mixture is evaporated to dryness and the residue recrystallized from water.

Output 2,47 g (81%).

So pl. 146-148aboutC.

P R I m e R 11. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(2-oxyethyl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide boiled in 30 ml of dioxane, in the presence 0,72 ml (0.12 moles) of 2-aminoethanol for 1 h under stirring. The reaction mixture was then evaporated to dryness and the residue recrystallized from methanol.

The output of 2.34 g (86%).

So pl. 146-148aboutC.

P R I m e R 12. 1-(5-Amino-3-dimethylamino-1H-1,2,4-triazole-1-yl)-N-(2-oxyethyl) carbothioamide.

2.17 g (0,01 mol) of methyl 1-(5-amino-3-dimethylene 1 h under stirring. Then the reaction mixture is cooled, isolated crystals are filtered off and recrystallized from 2-propanol.

Yield 1.89 g (82%).

So pl. 148-150aboutC.

P R I m e p 13. 1-(5-Amino-3-(4-methylpiperazine)-1H-1,2,4-triazole-1-yl)-N-(2 - oxyethyl)carbothioamide.

2,72 g (0,01 mol) of methyl 1-/5-amino-3-(4-methylpiperazine)-1H-1,2,4-triazole-1-yl) carbodiimide boiled in 10 ml of ethanol, in the presence 0,72 ml (0.12 moles) of 2-aminoethanol for 1 h under stirring. The reaction mixture is then cooled, isolated crystals are filtered off and recrystallized from 2-propanol.

Yield 2.50 g (88%).

So pl. 181-183aboutC.

P R I m e R 14. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(2-oxoprop-1-yl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide boiled in 30 ml of dioxane, in the presence of 0.92 ml (0.12 moles) of 2-oxypropylene for 2 h under stirring. Then the reaction mixture is evaporated to dryness and the residue will recrystallized from methanol.

Output 2,32 g (81%).

So pl. 135-137aboutC.

P R I m e R 15. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-2,2-dimethoxymethyl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-Tata for 2 h under stirring. Then the reaction mixture is evaporated to dryness and the residue was recrystallized from ethanol.

Yield 2.37 g (75%).

So pl. 134-135aboutC.

P R I m e R 16. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(2,2-dimethoxymethyl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide boiled in 20 ml ethanol in the presence of 1.3 ml (0.12 moles) of 2-aminoacetaldehyde for 4 h under stirring. Then the reaction mixture is cooled, the selected crystals are filtered and recrystallized from ethanol.

Output 2,80 g (83%).

So pl. 134-135aboutC.

P R I m e R 17. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(2-methoxyethyl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide boiled in 30 ml of dioxane, in the presence of 1.03 g (0.12 moles) of 2-methoxyethylamine for 4 h under stirring. Then the reaction mixture is evaporated to dryness and the residue will recrystallized from 2-propanol.

The output of 2.06 g (72%).

So pl. 103-105aboutC.

P R I m e R 18. 1-(5-Amino-3-methylthio-1H-1,2,4-triazole-1-yl)-N-(2-oxyethyl) carbothioamide.

2.20 g (0,01 mol) of methyl 1-(5-amino-3-methylthio-1H-1,2,4-triazole-1-yl)carbolit is the 12 o'clock Then the reaction mixture is evaporated to dryness in vacuum and the residue will recrystallized from acetonitrile.

The yield of 0.68 g (29%).

So pl. 131-132aboutC.

P R I m e R 19. 1-(5-Amino-3-morpholino-1H-1,2,4-triazole-1-yl)-N-(2-oxybutin-1-yl) carbothioamide.

2,59 g (0,01 mol) of methyl 1-(5-amino-3-morpholino-1H-1,2,4-triazole-1-yl)carbodiimide and stirred in 15 ml of dimethyl sulfoxide, in the presence of 0.95 ml (0.01 mole) of 2-aminobutanol at room temperature for 10 hours and Then 5 g of cracked ice and 10 ml of water is added to the reaction mixture, the selected product is filtered and recrystallized from isopropanol.

Output 0,69 g (23%).

So pl. 123-135aboutC.

P R I m e R 20. 1-(5-Amino-3-methylthio-1H-1,2,4-triazole-1-yl)-N-{3-/3-(1- piperidinylmethyl)phenoxy/propyl}carbothioamide.

2.20 g (0,01 mol) of methyl 1-(5-amino-3-methylthio-1H-1,2,4-triazole-1-yl)carbodiimide dissolved in 5 ml of dimethylsulfoxide, and then to the reaction mixture add 2,48 g (0,01 mol) 3-/3-piperidinylmethyl)-phenoxy/Propylamine cooling water. It is stirred at room temperature for 5 hours then added dropwise thereto a small amount of water (about 1 ml), highlighted the crystals are filtered and paracrystals-1,2,4-triazole-1-yl)-N-{3-/3-(1-piperidinylmethyl) phenoxy/propyl}carbothioamide.

1,74 g (0,01 mol) of methyl 1-(5-amino-1H-1,2,4-triazole-1-yl)carbodiimide dissolved in 10 ml of dimethyl sulfoxide, then add 2,48 g (0,01 mol) 3-/3-(1-piperidinylmethyl)-phenoxy/Propylamine. The reaction mixture was stirred at room temperature for 12 h, and then selected the crystals are filtered and recrystallized from ethanol.

The output of 1.57 g (42%).

So pl. 102-105aboutC.

P R I m e R 22. Tablets having the following composition is prepared in the pharmaceutical industry ways: Component Qty,

mg/tablet 1-(5-Amino-3-morpholino - 1H-1,2,4-triazole-1-yl)-N-3-/3-(1 - piperidinyl - methyl)phenoxy/propyl} carbothioamide 250 Lactose 61,8 Potato starch 43,2 Polyvinylpyrrolidone 22,5 Stearic acid Talc 9.0 to 13.5

The total mass of 400 mg

P R I m e R 23. Ointment having the following composition, get known in the pharmaceutical industry methods: Component Qty,

mg/tablet 1-(5-Amino-3-morpholino - 1H-1,2,4-triazole-1-yl)-N-3-/3-(1 - piperidinyl - methyl)phenoxy/propyl} carbothioamide 500 Ungentum hydrophilicum nonbomicum 10000

The active ingredient is in the external phase ointment, in a dissolved state.

P R I m e R 24. Suppositories having the following composition is prepared izvest-triazole-1-yl)-N-3-/3-(1 - piperidinyl - methyl)phenoxy/propyl} carbothioamide 100 Lecithin 48 Cera alba 96 cocoa Butter 1870 Distilled water 386

The total mass of 2500 mg

P R I m e R 25. Capsules having the following composition, is prepared by known methods in the pharmaceutical industry: Component Qty,

mg/tablet 1-(5-Amino-3-morpholino - 1H-1,2,4-triazole-1-yl)-N-3-/3-(1 - piperidinyl - methyl)phenoxy/propyl} carbothioamide 50 Lactose 119 Potato starch 10 magnesium Stearate 1

Total weight of 180 mg

DERIVATIVES of 1,2,4-TRIAZOLINONE General formula

< / BR>
where Q is hydrogen, (lower) allylthiourea, or a group of General formula N R1R2where R1and R2independently from each other hydrogen, lower alkyl or lower alkenyl, or R1and R2together with the nitrogen to which they are bound, form morpholino, piperidino or 4-methylpiperazine;

Y1WITH4-alkyl substituted by hydroxy or one or two1WITH4-alkoxygroup, di(C1WITH4)alkoxyphenyl(C1WITH4)alkyl or phenoxy(C1- C4)alkyl substituted on the phenyl ring WITH1WITH4-alkyl containing piperidinium,

or their pharmaceutically acceptable acid salt additive.

 

Same patents:

The invention relates to a new derivative of uracil with herbicide action

The invention relates to chemical-pharmaceutical industry, namely to new biologically active compounds on the basis of which can be created medicines that possess immunostimulating action

The invention relates to new biologically active pyridyl - or pyrimidinediamine derivative of piperazine or 1,4-disallocation, or their pharmacologically active acid additive salts with psychotropic action

The invention relates to a series of racemic and optically active derivatives of pyrido[1,2-a] pyrazine, which are used as antidepressants and anxiolytics, as well as intermediates of these derivatives

The invention relates to a method for obtaining complex diesters of alkyl substituted 4-hydroxy-piperidino connection of some complex organic esters, in particular to a method for producing a complex of diesters of alkyl-substituted 4-hydroxy-piperidino compounds of esters of dicarboxylic acids using a catalyst system containing the basic inorganic compound and a polar aprotic organic compound

The invention relates to the derivatives of pyrimidine, herbicide compositions and chemical method of weed control with their use

The invention relates to tetrahydropyrimidine derivative of formula (1) or their pharmaceutically acceptable salts, suitable as 3-HT3-capetronic antagonists:

(1) where Неt is a heterocyclic group, possibly substituted by 1-3 substituents selected from lower alkyl, lower alkenyl, lower quinil, group cycloalkyl-lower alkyl, arylalkyl, lower alkoxycarbonyl, halogen atom;

X represents a single bond attached to the carbon atom of the heterocyclic group

The invention relates to organic chemistry and relates to new compounds derived triethylcitrate

The invention relates to the chemistry of heterocyclic compounds, and in particular to an improved method for producing a 1-vinyl-1,2,4-triazole, which is used as a monomer for the synthesis of water-soluble and swollen polymers having valuable technical and biological properties

The invention relates to methods of producing substituted imidazole derivatives and their non-toxic pharmaceutically acceptable acid additive salts
Up!