Substituted 1,2,3-triazole


(57) Abstract:

The inventive use in medicine as agents against high blood pressure and in the treatment of heart failure in mammals. The product, substituted 1,2,3-triazole compounds of General formula I:


where R1- C2-6- alkyl, R2- carboxy - or tetrasociological; Reagent I: azide of formula II:

< / BR>
Reagent 2: alkane of the formula III, R1Reaction conditions: boiling reaction mixture. 3 table.

The invention relates to new substituted 1,2,3-triazole compounds, which can be used as agents against high blood pressure and in the treatment of heart failure in mammals.

Connection is proposed according to this invention inhibit the action of the hormone angiotensin II (AII) and therefore suitable for treatment caused by angiotensin hypertension. The enzyme renin acts on-globulin blood Plaza, angiotensinogen, with the formation of angiotensin I, which is then under the action of angiotensin-enzyme enters AII. The last connection is a powerful vazopressornye agent that causes high blood pressure in various what Subramaniam, inhibit the action of AII on its receptors on target cells, and thus prevents the increase in blood pressure. With the introduction of these compounds mammal suffering from hypertension, caused by the action of AII, the blood pressure decreases. These compounds are also suitable for the treatment of heart failure.

Pals et al. in irculation Research. 29, 673 (1971) described that the introduction of the rest of sarcosine in position 1 and alanine in position 8 of the endogenous vasoconstrictor hormone AII gives oktapeptid that blocks the action of AII on blood pressure goals rats. This analog [Sar1Ala8] AII, called "P-113", and then "Saralasin" is, as has been established, one of the most potent competitive antagonists of AII action, although, like most so-called peptide AII-antagonists, and has its own agonistic action. As shown, Saralasin lowers blood pressure in mammals and people, if high blood pressure is associated with circulating AII (Pals et al. irculation Research, 29, 673 (1971); Streeten and nderson, Handbook of pertension, T. 5, linical Pharmacology of Antihypertensive Drugs, A. E. Doyle (ditor), lsevier Sciene Publishers B. V. S. 246,1984). However, due to its agonistic properties, Saralasin usually manifests pricescope action is short and is only a problem when injecting, and oral introduction inefficiently. Although therapeutic use of peptide AII antagonists, such as Saralasin significantly limited due to their oral inefficiency and short time steps, their primary purpose is to serve the pharmaceutical standard.

According to the invention offers a substituted 1,2,3-triazole of the formula (I)

< / BR>
where R1C2-6-alkyl,

R2carboxy or tetrazolyl radical.

Especially preferred from the point of view antigipnoticescoe activity is


Detailed description of the invention

The new compounds of formula (I) can be obtained by using the reactions and techniques described in this section. The reaction is carried out in solvents corresponding to the used reagents and materials and are suitable for the reaction. The main source reagents for producing 1,2,3-triazoles are azides. Usage in this area of azides published several reviews, G. L. L'abbe', hem. Rev. 69, 345 (1969); T. Srodsky in "The Chemistry of the Azido Group", Wiley, New York (1971), S. 331. The most common and versatile method is thermal cycloaddition of azides to alkanal; N. Wamh functional groups in alkenovich and azide components, compatible with the reaction of thermal cycloaddition, as a rule, is determined by the availability of necessary precursors. Disubstituted 1,2,3-triazole(1) indicated in the reaction scheme below, can be obtained by heating alkyne (2) with azide (3). As a rule, receive the 1,4-isomer. However, it may be a mixture of 1,4 - and 1,5-regioisomers.

The reaction scheme

< / BR>
Example 1. Part a: Methyl-4'-azidomethyl-2-carboxylate.

To a solution of methyl-4'-bromomethylbiphenyl-2-carboxylate (5.0 g, 16.4 mol) in dimethylformamide (DMF) (40 ml) is added sodium azide (2.7 g, 41 mol). The mixture is stirred overnight at room temperature, and filtered. The filtrate is extracted with a mixture of water and ethyl acetate (100 ml). The aqueous phase is again extracted with ethyl acetate (100 ml), the combined organic phases are washed with water (3 x 100 ml), saturated aqueous sodium chloride (100 ml), then dried over magnesium sulfate, filtered and concentrated to an oil residue (3.9 g), which is used in subsequent reactions without further purification.

NMR (200 MHz; DCl3, TMS) :: 7,9 7,2 (m, 8H), 4,37 (s, 2H), 3,60 (s, 3H).

Part B: 4 - and 5-butyl-1-[(2'-carbomethoxybiphenyl-4-yl)methyl] -1,2,3-triazole.

A solution of methyl-4'-azidomethyl-2-carboxy what Aquum obtain 3.2 g of a yellow oily residue, from which you can select both isomers evaporative chromatography on neutral alumina (150 g, Activity I; 20% ethyl acetate/hexane).

Allot of 0.58 g of 4-isomer (high Rf) and 0.47 g of 5-isomer (low Rf);

NMR (4-isomer; 200 MHz; DCl3, TMS) :: 7,86 7,20 (m, N), of 5.55 (s, 2H), 3,63 (s, 3H), of 2.72 (t, J 7 Hz, 2H), 1,69 1,61 (m, 2H), 1,43 - of 1.26 (m, 2H), to 0.92 (t, J 7.5 Hz, 3H).

NMR (5-isomer; 200 MHz; DCl3, TMS) is identical to the 4-isomer except that the triplet at 2,72 hours per million is shifted to 2.54 per million hours.

Part b: 4-butyl-1-[2'-carboxyphenyl-4-yl)methyl] -1,2,3-triazole

To a solution of 480 mg (1.37 mol) of 4-butyl-1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-1,2,3-triazole in methanol (20 ml) is added 4N NaOH (20 ml). The resulting suspension is stirred at the boil under reflux for 2 to 6 hours (or until a homogeneous solution). The methanol is removed on a rotary evaporator and the residue was adjusted with water to a volume of 35 ml Titration to pH 4 with diluted Hcl get sticky residue, which is extracted with ethyl acetate. The organic residue is dried over magnesium sulfate, filtered, concentrated and receive 438 mg white solid connection, TPL90 95oC.

NMR (200 MHz; DCl3, CD3OD, TMS) :: 7,93 of 7.24 (m, N), 5,52 (s, 2H), 2,69 (t, J resol.

Similar to part b of example 1 from 5-butyl-1-[(2'-carboxymethylchitin-4-yl)methyl] -1,2,3-triazole (458 mg, 1.3 mol) receive 363 mg of the target product, TPL50 56oC.

NMR (200 MHz; DCl3TMS) :: of 7.96 7,13 (m, N), of 5.53 (s, 2H), 2,52 (t, J 7 Hz, 2H), 1,60 1,45 (m, 2H), 1,40 1,25 (m, 2H), of 0.85 (t, J 7 Hz, 3H).

Example 3. Part a: 4'-azidomethyl-2-(1-triphenyltetrazolium-5-yl) diphenyl.

This connection get similar to part a of example 1. From 4'-methyl bromide-2-(1-triphenylmethyl-2-tetrazol-5-yl)diphenyl (5.0 g, 9 mol) are obtained 4.5 g of the compounds in the form of a white solid connections.

NMR (200 MHz; CDCl3; TMS) :: 7,93 to 6.88 (m, N), 4,24 (s, 2H).

Part B: 4 - and 5-butyl-1-[2'-(1-triphenylmethanol-5-yl) diphenyl-4-ylmethyl]-1,2,3-triazole.

These compounds get similar part B of example 1. From 4'-azidomethyl-2-(1-triphenylmethanol-5-yl)diphenyl (4.5 g, 8,7 mol) gain of 5.4 g of crude isomers which purify by chromatography on silica gel (300 g, 50% diethyl ether/hexane).

Gain of 1.81 g of 4-butyl isomer: NMR (200 MHz; DCl3; TMS) :: 8,0 6,87 (m, 24N), to 5.35 (s, 2H), 2,60 (t, J 7.5 Hz, 2H), 1,51 1,59 (m, 2H), 1,38 1,27 (m, 2H), 0,89 (t, J 7 Hz, 3H).

Get 1,49 g of 5-butyl isomer, which has almost the same NMR spectrum for excluded the Part: 4-butyl-1-[2'-(1H-tetrazol-5-yl)diphenyl-4-ylmethyl] -1,2,3-triazole.

To a suspension of 4-butyl-1-[2'-(1-triphenylmethanol-5-yl) diphenyl-4-ylmethyl] -1,2,3-triazole (1.45 g, 2.4 mol) in water (15 ml) dropwise over several minutes, add a solution triperoxonane acid in water (1/1, 30 ml). The suspension is stirred for further 30 minutes and then alkalinized 4N NaOH (50 ml). The mixture is twice extracted with diethyl ether (100 ml), the aqueous phase is acidified to pH 4 4N HCl and get a white precipitate, which is filtered with suction, washed with water and hexane, dried under vacuum and receive 754 mg (87% ) of a white solid compound: NMR (200 MHz; CDCl3; TMS) :: to $ 7.91 - 7,00 (m, N), of 5.40 (s, 2H), 2,53 (t, J 7 Hz, 2H), 1,56 1,48 (m, 2H), 1,33 1,22 (m, 2H), 0,86 (t, J 7 Hz, 3H).

Example 4. 5-butyl-1-[2'-(1H-tetrazol-5-yl)diphenyl-4-yl-methyl] -1,2,3 - triazole.

This connection likewise get part b of example 3. In this case, acidification of the aqueous phase receive resinous residue that can be extracted with ethyl acetate. The organic layer is dried over magnesium sulfate, filtered, concentrated and get the specified white solid connection. 5-butyl-1-[2'-(1-triphenylmethanol-5-yl)diphenyl-4-yl-methyl] 1,2,3-triazole (1.4 g, 2.3 mol) obtain 600 mg (71%) of target compound. NMR (200 MHz; CDCl3, CD3OD, TMS) :: 7,78 7,06 (m, N), vs. 5.47 (s, 2H), 2,60 2,52 (t, J 8 Hz, 2H), 1,65 1,50 (m, 2H), 1.41 for the mu to the invention, obtained according to the methods of examples 1-4.


The hormone angiotensin II (AII) raises many biological reactions (e.g., compression of blood vessels) through the stimulation of its receptors on cell membranes. Upon identification of such compounds as AII antagonists that can interact with AII receptors, first assess the binding of the ligand-receptor. The evaluation is made according to the method described Glossman et al. in J. iol. hem. 249, 825 (1974), but with some modifications. Preparing a reaction mixture containing cortical microsome assay of adrenal glands of rats (source AII receptors) in Tris-buffer and 2 nm3N-AII c or without potential AII antagonist. This mixture is incubated for 1 h at room temperature and then the reaction being removed by rapid filtration and purification through a glass microfiber filter. Linked to the receptor3N-AII, delayed filter quantitatively measured with a scintillation counter. Inhibitory concentration (IC50) of potential AII antagonist, giving 50% replacement of the total number specifically associated 3H-AII is a measure of the affinity of these compounds to AII receptors (table.2).

Possible antihypertensi effect of the compounds, predlozhenie the left renal artery [Cagniano et al. J. Pharmacol. Exp. There. 208, 310 (1979)] In this method, the blood pressure increases due to the increase in renin production and subsequent increase in the concentration of AII. Compounds administered orally and/or intravenously through a cannula in the jugular vein. Arterial blood pressure continuously measure directly through the cannula in the carotid artery and recorded using a pressure transducer and recorder. Blood pressure after treatment compared with the pressure before treatment to determine antihypertensive steps compounds ( table.2).

Preparative form

Compounds of the invention can be used to treat hypertension, in any way, leading to the achievement of contact of the active ingredient from the impact site in the body of a warm-blooded animal. For example, administration can be parenteral, i.e., subcutaneous, intravenous, intramuscular or intraperitoneal. Besides or along with this, in some cases it is possible to conduct oral administration.

Connection, you can enter any means available, suitable for drugs, either individually as therapeutic agents or in combination with therapeutic agents. But, as a rule, they are administered with pharmaceutical carriers selected with regard to the way BB is tested antihypertensi effect of the compounds according to this invention, if the medication to enter in combination with compounds or prior to their introduction. The compounds can be used in combination with nonsteroidal anti-inflammatory drugs (NCPs), such as ibuprofen, indomethacin, piroxicam, naproxen, Ketoprofen, tolmetin, meclofenamate, sulindac and azapropazone to prevent damage to the kidneys, which sometimes happens when NSPs.

In this description under warm-blooded animals see animals having hemostatic mechanism, including mammals and birds.

Enter the dose depends on age, health and weight of the patient, severity of disease, type of concurrent treatment, frequency of administration and on the nature of the desired effect. The daily dose of the active ingredient will be about 0.5 to 500 mg/kg body weight. Typically, to achieve the desired result when one or more injections effective dose is 1 to 100, preferably 2 to 80 mg/kg / day.

The active ingredient can be entered orally in solid formulations, such as capsules, tablets, powders or liquid formulations, such as elixirs, syrups and suspensions. It can also enter parenterally, in sterile liquid preparative form.

Liquid formulation for oral administration can contain dyes and fragrances that facilitate the medication by the patient.

Suitable carriers for parenteral administration are, as a rule, water, a suitable oil, saline, aqueous solution of glucose (dextrose) and similar solutions of sugars and glycols, such as propylene glycol and polyethylene glycols. Solutions for parenteral administration preferably contain a water-soluble salt of the active ingredient, suitable stabilizers and, if necessary, buffer compounds. Suitable stabilizers Allawi. In addition, the use of citric acid and its salts, ethylenediaminetetraacetic acid (ETUC). Parenteral solutions can contain preservatives, such as benzylaniline, methyl - or propylparaben and chlorbutanol.

Suitable pharmaceutical carriers are described in Remington's Pharmacutical Sciences, A. Osol, a standard reference in this field.

Suitable pharmaceutical formulation for administration of the compounds may be illustrated as follows.


A large number of capsules produced by filling standard two-part, hard gelatin capsules, each containing 100 mg of powdered active ingredient, 150 mg of lactose, 50 mg of cellulose and 6 mg of magnesium stearate.

Soft gelatin capsules

Get a mixture of the active ingredient with a digestible oil such as soybean, cottonseed or olive oil, and injected with a pump of the positive displacement in gelatino obtaining soft gelatin capsules containing 100 mg of active ingredient. The capsules are washed and dried.


A large number of tablets get the regular ways and each preparative edirectories cellulose, 11 mg of starch and 98.9 mg of lactose. You can use the appropriate coatings to improve the taste or delay absorption.

Injectisome songs

A parenteral composition suitable for injection, is produced by stirring 1.5 wt. the active ingredient in about 10. propylene glycol. The solution is brought to final volume with water for injection and sterile.


Receive aqueous suspension for oral administration, where each 5 ml contain 100 mg of powdered active ingredient, 100 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution, U. S. P. and 0.025 ml of vanillin.

The technical progress achieved by the present invention is higher antigipnoticescoe activity by blocking the angiotensin II receptor, the compounds in accordance with the present invention compared to the compounds known previously. The only known receptor antagonists of angiotensin II are described in U.S. patents 4,207,324, 4,355,040 and 4,340,598, as well as in the application PCT 103647 author Takeda. The most effective compounds in accordance with these patents were subjected to the same pharmacological tests that connection, receiving the nnye evidence suggests, what is known compounds have very low antigipnoticescoe activity with little affinity for the receptor binding of angiotensin II.


Substituted 1,2,3-triazoles of General formula

< / BR>
where R1WITH2C6-alkyl;

R2-carboxyl or tetrasociological.


Same patents:

The invention relates to indole derivative of General formula (l):


where R and R1such that:

or R and R1the same or different hydrogen atom, a straight or branched lower alkyl, cycloalkyl to 6 carbon atoms;

or R and R1together with the nitrogen atom to which they are bound, form a piperazinil, substituted lower alkyl,

A -:

or chain /CH2/n, where n can take the values 2 or 3,

or circuit< / BR>
X and Y or each a hydrogen atom,

or one hydrogen atom and the other is a hydroxy radical or1-C4-alkyl,

or X and Y together form an oxo radical, a radical alkyltin with 1-4 carbon atoms or a radical N-OR5where R5a hydrogen atom or an alkyl radical with 1-4 carbon atoms, the substituents a, b, c, d such that:

either each hydrogen atom,

or a and b together form a function oxo and C and d are each a hydrogen atom;

Z -:

or a hydrogen atom,

or a moiety of the lower alkyl or the group aminoalkyl formula:


where R2lowest alkylen;

moreover, these compounds of formula (I) can nachtergaele or organic acids

The invention relates to new biologically active chemical compounds, in particular to cyclic amino compounds of the formula I

BANwhere In - perederina, piperidinyl or pyrrolidinyl group, each of which may be substituted by a lower alkyl group, lower alkylcarboxylic group, carbobenzoxy, afterburner (lower) accelgroup, phenylketone (lower) alkyl group, phenylcarbamoyl (lower) alkyl group or phenyl (lower) alkyl group, each of which may be substituted by a halogen atom or a lower alkoxygroup; p is 1 or 2; And -- is a bond, or two-, or trivalent aliphatic C1-6hydrocarbon residue which may be substituted by a lower alkyl group, oxo, hydroximino or hydroxy-group;means either simple or double bond, provided that when a represents a bond, thenmeans of a simple bond; R2and R3independent means ATO condition, both R2and R3are not hydrogen atoms, or R2and R3together with the adjacent nitrogen atom form piperidino, hexamethyleneimino, morpholino, pyrolidine, pieperazinove or 1-imidazolidinyl group, each of which may be substituted by a lower alkyl group, a phenyl (lower) alkyl group, a lower alkylcarboxylic group or diphenyl (lower) alkyl group or a physiologically acceptable salt additive acid

The invention relates to new imidazole derivative of General formula I

where R1-COOH or the group< / BR>
R2=H-C3H7or n-C4H9;

R3-Cl, CF3C2F5C6H5or COOH;

R4-COOH, CHO, or CH2HE, provided that

a) when R4-CH2OH, R3-C2F5and R2-n-C3H7,

b) when R3-COOH, R4also is COOH,

b) when R2-n-C3H7, R3-C2F5and R4-COOH, R1is the groupwhich inhibit the action of the hormone angiotensin and can be used in medicine

Derived sulphides // 2060993
The invention relates to intermediate products to obtain new derivatives of cephalosporin

FIELD: chemistry.

SUBSTANCE: present invention refers to the new naphtylene derivative having general formula (I-A) and to their pharmaceutically acceptable salts having the property of inhibition of the cytochrome ferment P450RAI (Cyp26) activity, to the pharmaceutic composition thereof and to the method of inhibition of cytochrome ferment P450RAI (Cyp26). , wherein X is selected from imidasolyl or triasolyl; R2 and R3, independently represent H, C1-10-alkyl; G1 is -NR72R82 or G1 and R3 taken together with attached carbon atom form 3-10-membered saturated ring or heterocyclic saturated ring containing N as heteroatom which is optionally substituted with substituting group R72, Z, R4b, R5b, Q1, R72, n2, n3 and n4 values are indicated in the formula of the invention.

EFFECT: present invention refers to the intermediates for compounds with general formula (I-A) and to their pharmaceutic salts thereof.

37 cl, 30 dwg, 7 tbl

FIELD: agriculture.

SUBSTANCE: they use 2-(1H-1-pyrrolyl)-4-dipropylamino-6-(4-ethoxycarbonyl-5-methyl-1,2,3-triazole-1-yl)-1,3,5-triazine (PDET) with the following formula: , as antidote against phytotoxic effect of herbicide of 2,4-dichlorophenoxyacetic acid at germinated sunflower seeds.

EFFECT: increased length of roots and hypocotyl of germs.

1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula I where A represents an optionally substituted aryl or heteroaryl, B - a benzene or thiophene cycle, C - a benzene or aliphatic hydrocarbon cycle, while values of other radicals are disclosed in the description. The compound according to the present invention, and the based pharmaceutical compositions exhibit a strong antagonistic effect in relation to GnRH receptor that makes them applicable for treatment of GnRH-related diseases, particularly prostate cancer, benign prostatic hyperplasia, breast cancer, endometriosis and/or uterine fibroid tumour.

EFFECT: improved clinical effectiveness.

11 cl, 70 tbl, 765 ex

FIELD: chemistry.

SUBSTANCE: invention describes N-cycloalkylbenzylamide derivatives of formula

, where A denotes a saturated 5-member heterocyclic group, Z1 denotes a substituted C3-C7-cycloalkyl; Z2 and Z3, which can be identical or different from each other, denote a hydrogen atom; C1-C8-alkyl; cyano; C1-C8-alkoxycarbonyl; a method of producing said compounds, use thereof as fungicidal active substances, particularly in form of fungicidal compositions, and method of controlling phytopathogenic fungi, mainly in plants, using said compounds or compositions.

EFFECT: higher activity, low amount of active substance while maintaining efficiency at least equivalent to that of existing compounds.

11 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to methods and reagents of labelling a vector such as a peptide, involving reaction of a compound of formula

with a compound of formula R*-L2-N3 (II) in the presence of a Cu (I) catalyst.

EFFECT: obtained labelled conjugates are useful as diagnostic agents, for example, as radiopharmaceutical preparations, more specifically for use in positron emission tomography (PET) or single-photon emission computed tomography (SPECT) or for radiotherapy.

7 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: agent having fungicidal activity, containing substituted ethyl(1,2,3-triazol-4-yl) dinitro acetates of formula Ia-c:

, where Ia, b R=CH3, R1=H; Ic R=H; R1=CH3 in concentration of 30 mg/l.

EFFECT: high efficiency.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: described is a method of producing triazolino[4',5':1,2]fullerene[60] of formula (1): involving reaction of fullerene C60 with hydrazoic acid (HN3), produced in situ by reacting NaN3 and H2SO4, taken in molar ratio C60:NaN3:H2SO4=1:(100-120):(100-120), in chlorobenzene at temperature 40C for 2-4 hours with output 8-17%.

EFFECT: end product can be used as a complexing agent, sorbent, biologically active compound and when producing novel materials with given properties.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-cycloalkylbenzyl thiocarboxamides or N-cycloalkylbenzyl-N'-substituted carboxyimide amide derivatives of formula (I):

wherein A is a carbo-bound, unsaturated 5-member heterocyclic group selected from pyrazolyl, pyrrolyl, triazolyl and furanyl, and which can be substituted with up to four substitute groups R; T is S; Z1 is unsubstituted C3-C7-cycloalkyl or C3-C7-cycloalkyl, substituted with up to 2 substitutes which can be identical or different and which can be selected from a list consisting of C1-C8-alkyl groups; Z2 and Z3, which can be identical or different, are a hydrogen atom or C1-C8-alkyl; X, which can be identical or different, is a halogen atom; C1-C8-alkyl; C1-C8-halogenalkyl, containing up to 3 halogen atoms which can be identical or different; C1-C8-halogenalkoxy, containing up to 3 halogen atoms which can be identical or different; C3-C7-cycloalkyl; tri(C1-C8-alkyl)silyl; tri(C1-C8-alkyl)silyl-C1-C8-alkyl; benzyloxy, phenoxy, which can be substituted with up to 2 substitute groups Q; phenyl, which can be substituted with up to 2 substitute groups Q; or two substitutes X together with the next carbon atoms to which they are bonded form methylene dioxo; n is 1, 2 or 3; R, which can be identical or different, is a hydrogen atom; a halogen atom; C1-C8-alkyl; C1-C8-halogenalkyl, containing up to 3 halogen atoms which can be identical or different; Q, which can be identical or different, is a halogen atom; as well as agriculturally acceptable salts thereof. The invention also relates to a fungicidal composition containing an effective amount of the compound of formula (I) as an active ingredient.

EFFECT: novel compounds which can be used in agriculture for plant pathogenic fungi control are obtained.

7 cl, 1 tbl, 56 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing novel hydrazones of nitro-1,2,3-triazol-4-yl carbaldehyde of general formula Ia and Ib , where Ia, R=H, R1=CH3O2C; Ib R=CH3, R1=H; by reacting 4-trinitromethyl-1,2,3-triazole of general formula II , where R and R1 assume values given above, with an equimolar amount of 1,1-diphenyl hydrazine while stirring in dry ethoxyethane at 0C and holding the mixture at said temperature for 2 hours.

EFFECT: compounds can be used as potential fungicidal agents.

1 cl, 2 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are novel aminitriazole derivatives of formula (I), where A is phenyl, heterocyclyl or propan-1,3-diyl; E is *-C1-4alkyl-O-, -CH=CH- or , where asterisks stand for bond, through which binding with R1; Q- O or S occurs; R3 is hydrogen, C1-4alkyl, cyclopropyl, C1-4alkoxy-C1-4alkyl, benzyl or -CH2CH2C(O)O-tert-Bu; R1 is pyridyl or phenyl, possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, C1-4fluoroalkyl, C1-4fluoroalkoxy, di-( C1-3alkyl)amino or C1-4alkoxy-C1-2alkyl; and R2 is -CO-C1-3alkyl,-CF2-C1-3alkyl or -SO2-C1-3alkyl; or their pharmaceutically acceptable salts, pharmaceutical composition, which contains them.

EFFECT: obtaining novel compounds for treatment of inflammatory disease or Alzheimer's disease.

20 cl, 105 ex, 1 tbl

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

and their pharmaceutically acceptable acid-additive salts wherein X means a ordinary bond or ethynediyl group; when X means ordinary bond then R1 means halogen atom, (lower)-alkyl, (lower)-alkylcarbonyl, (lower)-cycloalkyl, benzoyl, phenyl substituted optionally with halogen atom, hydroxyl, (lower)-alkyl, (lower)-alkoxy-group, halogen-(lower)-alkoxy-group or cyano-group; styryl, phenylethyl, naphthyl, diphenyl, benzofuranyl, or 5- or 6-membered heterocyclic ring representing thiophenyl, furanyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl which are optionally substituted; when X means ethynediyl group then R1 means hydrogen atom, (lower)-alkyl substituted optionally with oxo-group; (lower)-cycloalkyl substituted with hydroxyl; (lower)-cycloalkenyl substituted optionally with oxo-group; (lower)-alkenyl, optionally substituted phenyl; 5- or 6-membered heterocyclic ring representing thiophenyl, thiazolyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl or dihydropyranyl and substituted optionally; R3 means phenyl, pyridyl, thiophenyl or thiazolyl which are substituted optionally. These compounds can be used for treatment or prophylaxis of acute and/or chronic neurological diseases, such as psychosis, schizophrenia, Alzheimer's disease, disorder of cognitive ability and memory disorder. Also, invention describes a medicinal agent based on these compounds and a method for preparing compounds of the formula (I).

EFFECT: improved method for preparing, valuable medicinal properties of compounds.

10 cl, 1 tbl, 173 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepines of the general formula (I):

wherein X means ordinary bond or ethynediyl group wherein if X mean ordinary bond then R1 means halogen atom or phenyl substituted with halogen atom optionally or (C1-C7)-alkyl group; in case when X means ethynediyl group then R1 mean phenyl substituted with halogen atom optionally; R2 means halogen atom, hydroxy-group, lower alkyl, lower alkoxy-group, hydroxymethyl, hydroxyethyl, lower alkoxy-(ethoxy)n wherein n = 1-4, cyanomethoxy-group, morpholine-4-yl, thiomorpholine-4-yl, 1-oxothiomorpholine-4-yl, 1,1-dioxothiomorpholine-4-yl, 4-oxopiperidine-1-yl, 4-(lower)-alkoxypiperidine-1-yl, 4-hydroxypiperidine-1-yl, 4-hydroxyethoxypiperidine-1-yl, 4-(lower)-alkylpiperazine-1-yl, lower alkoxycarbonyl, 2-di-(lower)-alkylaminoethylsulfanyl, N,N-bis-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, (lower)-alkylcarboxy-(lower)-alkyl, lower alkoxycarbonylmethylsulfanyl, carboxymethylsulfanyl, 1,4-dioxa-8-azaspiro[4,5]dec-8-yl, carboxy-(lower)-alkoxy-group, cyano-(lower)-alkyl, 2-oxo[1,3]dioxolane-4-yl-(lower)-alkoxy-group, 2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrole-5-yl, (3R)-hydroxypyrrolidine-1-yl, 3,4-dihydroxypyrrolidine-1-yl, 2-oxooxazolidine-3-yl, carbamoylmethyl, carboxy-(lower)-alkyl, carbamoylmethoxy-, hydroxycarbamoyl-(lower)-alkoxy-, lower alkoxycarbamoyl-(lower)-alkoxy-, (lower)-alkylcarbamoylmethoxy-group; R3 means phenyl, thiophenyl, pyridinyl that are substituted with halogen atom, cyano-group, carbamoyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl wherein groups of 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl are substituted optionally with (C1-C7)-alkyl or (C1-C7)-alkylsulfanyl, and to their pharmaceutically acceptable salts. Also, invention describes a medicinal agent that is antagonist of mGlu receptors of the group II based on compound of the formula (I). The medicinal agent can be used in treatment and prophylaxis of acute and/or chronic neurological disturbances including psychosis, schizophrenia, Alzheimer's disease, disturbances in cognitive ability and memory damage.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 98 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing pyrimidinone compound of the formula (1) and its salts. Method involves thioamidation reaction of compound of the formula (7) with using Lavesson's reagent followed by treatment of the reaction product with alcoholic reagent as shown in the following reaction scheme 2: (7) → (1) wherein R1 represents (C1-C4)-alkyl with linear or branched chain; R2 represents (C1-C4)-alkyl with linear or branched chain; R3 and R4 represent (C1-C4)-alkyl with linear or branched chain; n is a whole number taken among 1, 2, 3, 4, 5 and 6. Invention provides preparing pyrimidinone compound of the formula (1) by relatively simple and high-effective method. Also, invention relates to pyrimidinone trihydrate compound of the formula 91).

EFFECT: improved preparing method.

10 cl, 2 tbl, 5 ex