10-methoxy-5 - methyl-6- (1',1'- dioxido-2'- metalorganics -3'- hydroxy -4'-methoxybenzo(c)thiophene - 7 - yl) -5h-3,4,6,7 - tetrahydrofuro [4.3.2-q] [3]benzazocin with an antidepressant

 

(57) Abstract:

Usage: in medicine, in particular as antidepressant agents. The inventive product - 10-methoxy-5-methyl-6 - 1,1-dioxido-2-meta-chlorvinyls - 3-hydroxy-4-methoxybenzo[b] thiophene-7-yl)-5h-3,4,6,7-tetrahydrofuro[4, 3, 2, -Q][3]-benzazocin, BF C19H26ClN3O6, yield 80% , so pl. 205-208C. Reagent 1: (10-methoxy-6 - 4-methoxy - 1, 1, 3 trioxo - 2, 3-dihydrobenzofuranyl 7 , methyl-3, 4, 6, 7-tetrahydro-5h-furo[4, 3, 2 - Q][3])-benzazocin). Reagent 2: diazonium salt derived from a meta-Chloroaniline and sodium nitrite in aqueous HCl. Conditions of reactions: azo coupling in a mixture of pyridine and water at 5C and then at room temperature. table 4.

The invention relates to new chemical compound, particularly to a 10-methoxy-5-methyl-6-(1', 1'-dioxido-2' -meta-chlorvinyls-3'-hydroxy-4' -methoxy-benzo[b] thiophene-7-yl)-5H-3,4,6,7-tetrahydro[4,3,2-Q]-[3]benzazocine formula

(I) with an antidepressant.

The specified connection and its properties are not described in literature. State registration number - 10258691.

Despite the presence of a large group of substances that have a positive impact on the emotional state of patients, Stroganova action continues unabated. This is due to relatively slow (5-10 days) the onset of therapeutic effect of drugs, and a slight decrease in the intensity of various neurotic disorders many known drugs, and the presence of serious side effects (cardiotoxic action of tricyclic antidepressants, anticholinergic activity imizine). In addition, an important side effect of antidepressants is incompatibility with other drugs some food (1).

Similar in structure to the claimed compounds is galantamine (nivalin) is a reversible inhibitor of cholinesterase (2) formula

< / BR>
Analogous to the properties of the claimed compounds is imison (melipramin) formula

< / BR>
The aim of the invention is the search for new derivatives benzazocine having a stimulating effect on the Central nervous system and have advantages over the known analogues. This goal was achieved by a new 10-methoxy-5-methyl-6-(1' ,1' -dioxido-2-metalorganics-3-hydroxy-4' -methoxy-benzo [b]thiophene-7' -yl)-5H-3,4,6,7-tetrahydro - furo[4,3,2,Q] [3] benzazocine formula I with an antidepressant. The method of obtaining Mgr-7 )-5-methyl-3,4,6,7-tetrahydro-5H-furo[4,3,2, Q] [3] benzazocine with a diazonium salt derived from m-Chloroaniline and NaNO2in aqueous HCl according to the method 3

< / BR>
Acute toxicity and antidepressant effects of the compounds were studied in the laboratory of new drug chemistry Institute and Department of biochemistry, Ural branch of the USSR Academy of Sciences. In table. 1 shows the acute toxicity of the studied compounds and the most widely used antidepressants.

From the data table. 1 shows that compound 1 is 4-7 times less toxic than used in medical practice antidepressants. The substance 1 belongs to the 3rd class of mild-hazard substances.

The antidepressant activity of the proposed compounds were studied in outbred mice weighing 16-18 g On the effects of the compounds on the Central nervous system to be judged by the change in the estimated reactions, duration of sleeping pills, apomorfina and fenaminovoj stereotypia, time of immobilization, the effect on emotional status and aggressiveness.

The investigated compound was administered orally in a dose of 5 mg/kg Antidepressant effect of a substance compared with the effect melipramin entered in the dose of 10 mg/kg) and amitriptyline entered in the dose of 10 mg/kg the results of the IP is eacli on the horizontal test, but the number of vertical stevani 3 times higher than the activity of animals in the control group, as well as melipramine and amitriptyline analogous properties.

In table. 3 shows data on the impact of the new framentation on the duration of the hypnotic effect of barbiturates (chloral hydrate and geksenala, and duration fenaminovoj and apomorfina stereotypie.

From the data table. 3 shows that the studied compound potentional effect sleeping pills - geksenala 1.3 times, chloralhydrate 3 times, which indicates the presence of a sedative component. The effect of compounds on the duration of action of barbiturates than the effect of amitriptyline and melipramin. The target compound is also potentiality action of amphetamine and apomorphine, which apparently is associated with the stimulation of serotonin and apomorphine receptors.

In table. 4 shows the effect of compound 1 on the emotional status of the animal, aggressiveness, defined by the method of provocation and electrovalves irritation (4), and change the time of immobilization test "hanging by the tail" (5).

From the data table. 4 shows that the studied compound 1 does not change the emotional status of IPO test "hanging by the tail" so, unlike imizine has no timolepticheskoe action. An additional argument in favor of the existence sedative effect of the claimed compounds is 1.5 times lower voltage necessary for the emergence of aggressive response than melipramin (imizine).

Thus, 10-methoxy-5-methyl-6-(1,1-dioxido-2-metalorganics-3-hydro - XI-4-methoxybenzo [b] thiophene-7-yl)-5H-3,4,6,7-tetrahydrofuro[4,3,2 Q] [3] benzazocin connection moderately toxic, the range of actions on the Central nervous system has a pronounced anti-depressive effect, accompanied sedative effect. The proposed connection is active at its introduction in doses 10 times smaller (LD50compared with the known antidepressants.

P R I m e R 1. Synthesis of 10-methoxy-5-methyl-6-(1' ,1' -dioxido-2' -metalorganics-3-hydroxy-4' -methoxybenzo[b] thiophene-7' -yl)-5H-3,4,6,7-tetrahydrofuro[4,3,2,Q][3] benzazocine (1).

To a solution of 0.44 g (0.001 mol) of 10-methoxy-6-(4' -methoxy-1' ,1' ,3' -trioxo-2 ,3-dihydrobenzo[in]thienyl-7' )-5-methyl-3,4,6,7 - -tetrahydro-5H-furo[4,3,2, Q] [3] benzazocine in a mixture of 10 ml of pyridine and 10 ml of water in 5aboutWith bury 20 ml of diazonium salt (10,8 ml HCl, 18 ml of water, 1.1 g of meta-Chloroaniline, 0.6 g NaNO<, the content of inorganic fillers layer was washed with water, brine, dried MgSO4, was evaporated in a water jet vacuum pump, the residue was led from ethyl acetate. Got 0,46 g (80%) substance (1). So pl. 205-208aboutC. the IR spectrum (cm-1): 720, 780, 1025, 1065, 1080, 1120, 1145, 1210, 1265, 1275, 1295, 1339, 1510, 1580, 1600, 1620, 1670, 3520.

Range of the MRP , M. D.): 2,45 (3H, NMe), 2.85 m (4N, N4,6,7 there), 3.50 m (2N, N3), of 3.94 (3H, OMe), of 3.97 (3H, OMe), 6,77 DD (2N , N8,9), 7,05 m (4H, Ph and 2N, N5,6), 7,98 (1H, H2).

Found, %: C To 59.9; H 4,8; N 7,5; CL 6,4; S 5,2.

WITH29H26ClN3O6S.

Calculated, %: C 60,0; N 4,5; N 7,1; Cl 6,1; S 5,5.

P R I m m e R 2. The impact of the proposed connection on the estimated reaction was studied on 28 animals provided intraperitoneal administration. The target substance was administered at doses of 5.0 mg/kg, the activity of the compounds was compared with the activity of melipramin and amitriptyline entered in doses of 10.0 mg/kg of this compound does not change the estimated response for the horizontal test compared with the control group, whereas amitriptyline and melipramin increase them. Vertical test substance 1 increases the estimated response to 16.9 for 1 min, whereas in the control group the number of vertical separato studied 56 animals. Geksenal or chloral hydrate was administered intraperitoneally in doses of 75.0 or 300 mg/kg, respectively. The target compound was administered orally in a dose of 5.0 mg/kg Duration chloralhydrate sleep with the introduction of the connection 1 is 280 rpm, 3.5 times more than in the control group. Duration geksenalovy sleep with the introduction of the claimed compounds is increased by 1.3 times compared with the control group.

P R I m e R 4. The impact of the proposed connection on serotonin and dopamine receptors studied by changing the length fenaminovoj and apomorfina stereotypie. Studies were performed on 48 animals. Apomorphine was administered at a dose of 20 mg/kg of amphetamine in the dose of 10 mg/kg subcutaneously 1 h after injection of compound 1 oral dose of 5.0 mg/kg Study the connection increases the duration fenaminovoj and apomorfina stereotypie. Time of action of apomorphine with the introduction of the substance 1 is 65 min, amphetamine - 155 min in the control group, 60 min and 125 min, respectively.

P R I m e R 5. The impact of the proposed connection on the emotional status was assessed by the level of stress during capture of the animal by hand (on a 3 - point scale). The amount of emotional stress at wanee of the studied compounds on the aggressiveness of the animals was performed by the method of provocation - electrobalance irritation when passing a pulsed electric current through the electrode the floor of the chamber with animals (2) (5). As considered the first signs of reaction of animals to irritation. With the introduction connections 1 aggressiveness of animals occurred at a voltage of 81, whereas in the control group this value is 57 Century.

P R I m e R 7. The influence of the proposed connection on the immobilization of animals studied on the test "hanging by the tail, by the method (6). With the introduction of a substance at a dose of 5.0 mg/kg compound practically does not change the immobilization time (190 min connection (1) - 192 rpm control).

10-Methoxy-5-methyl-6-(1', 1'-dioxido-2'-metalorganics-3'-hydroxy - 4'-methoxybenzo(b)thiophene-7-yl)-5H - 3,4,6,7-tetrahydrofuro[4.3.2-Q] (3)benzazocin formula

< / BR>
with an antidepressant.

 

Same patents:

The invention relates to a method for producing novel compounds that have biological activity similar to the activity retinova acid, more specifically, to methods and intermediate products used in the synthesis dogsleding acetylene compounds with similar retinova acid activity

The invention relates to a method for producing new derivatives benzocycloheptene acids

The invention relates to pharmaceutical industry and relates to a method of obtaining a crystalline sodium salt of 5-chloro-3-(2-thenoyl)-2-oxindole-1-carboxamide

FIELD: organic synthesis.

SUBSTANCE: invention provides compounds of general formula I:

, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.

EFFECT: increased choice of cysteine protease inhibitors.

34 cl, 1 tbl, 13 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a new compound of the general formula (2) and a method for its preparing wherein R1 represents hydrogen atom or salt-forming metal; R2 represent a direct or branched (C1-C7)-halogenalkyl group; m represents a whole number from 2 to 14; n represents a whole number from 2 to 7; A represents a group taken among the following formulae: (3) , (4) ,

(5) ,

(6) ,

(17) , (18) , (19) , (20) , (23) , (25) and (26) wherein R3 in formula (6) represents a direct or branched group (C1-C5)-alkyl group; R8 in formulae (18) and (20) represents a direct or branched (C1-C5)-alkyl group, a direct or branched (C2-C5)-alkenyl group or a direct or branched (C2-C5)-alkynyl group; in formula (23) each R21, R22, R23 and R24 represents independently hydrogen atom, a direct or branched (C1-C5)-alkyl group, a direct or branched (C1-C7)-halogenalkyl group, halogen atom or acyl group; in formulae (25) and (26) X represents halogen atom; or enantiomers of compound, or hydrates, or pharmaceutically acceptable salts of compound, or its enantiomers. Also, invention relates to a pharmaceutical composition containing indicated compound as an active component and to a therapeutic agent used against breast cancer based on thereof.

EFFECT: valuable medicinal properties of compounds.

10 cl, 2 tbl, 39 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new biphenylsulfonylcyanamides of the formula (I): wherein R1 means: 1. (C1-C8)-alkyl; 4. -CnH2n-nn-Y wherein nn = 0 or 2 and n = 0-4, and n is not 0 or 1 if nn = 2; 5. CnH2n-nn-Y wherein nn = 0 or 2 and n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with amino-group or NR(22)R(23); R2 means: 2. (C1-C)-alkyl; 4. (C2-C12)-alkenyl; 5. (C2-C8)-alkynyl; 6. -CnH2n-nn-Z wherein nn = 0 or 2; n = 0-4, and n is not or 1 if nn = 2; 7. -CnH2n-nn-Z wherein nn = 0 or 2; n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with a residue taken among a series: 1. phenyl; 3. NR(22)R(23); 5. COOR(16); R3 and R4 mean hydrogen atom; R5, R6 and R7 mean independently of one another hydrogen atom (H), (C1-C8)-alkyl; SO2-(C1-C4)-alkyl, F, Cl, Br, J, OR(10) wherein R(10) means hydrogen atom, (C1-C4)-alkyl that is substituted if necessary with methoxy- or ethoxy-group; R(9) means OR(13) wherein R(13) means hydrogen atom, H,(C1-C8)-alkyl;X means carbonyl group, -CO-CO- or sulfonyl group; Y and Z mean independently of one another: 1. phenyl, 1-naphthyl, 2-naphthyl; 2. one of residues determined in cl. 1 substituted with 1-5 similar or different residues taken among a series: phenyl, F, Cl, Br, J, CF3, SOqR(18), OR(16), NR(19)R(20), -CN, NO2, COR(9), or two residues form methylenedioxy-group; 3. furyl, thienyl, pyridyl, benzimidazolyl, indolyl, benzothiophenyl, dihydroquinazolinyl; 5. (C3-C10)-cycloalkyl wherein cyclopropyl, cyclopentyl, cyclohexyl and indalyl are preferable; 6. one of residues determined in cl. 5 substituted with phenyl; R(16) means: 1. hydrogen atom; 2. (C1-C4)-alkyl; 3. (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; R(19) and R(20) mean independently: hydrogen atom (H), (C1-C4)-alkyl; R(22) and R(23) mean independently of one another hydrogen atom (H) or CO-OR(24) wherein R924) means -CnH2n-phenyl wherein n = 1-4; q = 2; and their physiologically acceptable salts. Compound of the formula (I) inhibit sodium-dependent chloride-bicarbonate exchange "NCBE".

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

4 cl, 2 tbl, 568 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compositions eliciting an antilipidemic effect and comprising inhibitor of bile acid transport in jejunum of the general formula (I): and inhibitor of HMG-CoA-reductase. Also, invention relates to a method for carrying out the combined therapy.

EFFECT: improved treatment method, valuable medicinal properties of compositions.

15 cl, 9 tbl, 1401 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

22 cl, 1 tbl, 2 sch, 78 ex

FIELD: organic chemistry, pharmaceutical industry, medicine.

SUBSTANCE: invention relates to new derivatives of S-substituted N-1-[(hetero)aryl]alkyl-N'-1-[(hetero)aryl]alkylisothioureas of general formula I

in form of free base and salts with pharmaceutically accepted acids, as well as racemate, individual optical isomers or mixture thereof. In formula R1, R2, R3, R4, Y and Z are as described in specification. Compounds of present invention are capable to potentiate (positively modulate) AMPA/KA glutamate receptors and simultaneously to block transmembrane currents induced by activation of NMDA glutamate receptors. Also disclosed are method for production of said compounds, including optical isomers; pharmaceutical composition; method for investigation of glutamatergic system, and method for Alzheimer's disease, treatment; as well as method for extreme retentiveness of memory by administering of effective amount of claimed compounds.

EFFECT: new pharmaceutically active compounds for Alzheimer's disease treatment.

23 cl, 1 tbl, 11 ex

FIELD: pharmaceutical industry, in particular new bioactive chalcones.

SUBSTANCE: invention relates to new chalcones of formula I

, pharmaceutically acceptable salts or solvates thereof, wherein Ar is optionally substituted C5-C10-carbocycle group or 5- or 6-membered heterocycle group having sulfur atom in cycle, and Ar substituents are selected independently from Cl, Br, F, CN, SCH3 and OR10, wherein R10 is linear or branched C1-C6-hydrocarbon; R is OH or R10; R2 and R3 are independently phenyl, saturated linear or branched C1-C6-hydrocarbon, or R2 and R3 together with carbon atom attached thereto form 5- or 6-membered carbocycle group with the proviso, that in compounds where R is OH and both R2 and R3 are methyl, Ar is not phenyl, 4-chlorophenyl, 4-chlorophenyl, 4-methylphenyl, 2-chlorophenyl, 3,4-dimethoxyphenyl, or 4-methoxyphenyl. Also disclosed are drug component for treatment or prophylaxis of neoplasm and pharmaceutical compositions with antiproliferation effect based on compounds of formula I.

EFFECT: new chalcone derivatives with value bioactive action.

26 cl, 2 tbl, 22 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new lipoic acid derivatives of general formula Ia

1, wherein n = 0-4, integer; -X-Y represents -O(CH2)r-, -CO-N(R3)-(CH2)r-, -N(R4)-CO-(CH2)r; -X'-Y' represents -(CH2)r-, -(CH2)r-N(R3)-(CH2)r-, -(CH2)r-CO-N(R3)-(CH2)2-; R3 and R4 are the same or different and represent hydrogen or alkoxycarbonyl; r = 0-4, integer; Ω represents piperazinyl, piperidyl or phenyl. Also disclosed are method for production the claimed derivatives and pharmaceutical composition, containing the same. Compounds are useful as NO-syntase inhibitors and/or reagents mediating redox state of thiol groups.

EFFECT: new lipoic acid derivatives.

7 cl, 17 ex

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used in stomatology in the topical anesthesia. The pharmaceutical composition comprising articaine hydrochloride and epinephrine hydrochloride and accessory substances, such as sodium metabisulfite, sodium chloride and water for injection involves additionally glycine and pH-regulating substance taken in the definite ratio of components. Invention provides preparing the preparation that is stable, non-toxic and doesn't cause allergic response reactions and elicits highly expressed infiltration and conducting anesthetic activity, good tissue tolerance and activity promoting to accelerated wound-healing in the post-operative period.

EFFECT: improved and valuable medicinal properties of composition.

3 cl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of carboxylic acids of the formula: wherein Y is taken independently in each case among the group comprising C(O), N, CR1, C(R2)(R3), NR5, CH; q means a whole number from 3 to 10; A is taken among the group comprising NR6; E is taken among the group comprising NR7; J is taken among the group comprising O; T is taken among the group comprising (CH2)b wherein b = 0; M is taken among the group comprising C(R9)(R10), (CH2)u wherein u means a whole number from 0 to 3; L is taken among the group comprising NR11 and (CH2)n wherein n means 0; X is taken among the group comprising CO2H, tetrazolyl; W is taken among the group comprising C, CR15 and N; R1, R2, R3 and R15 are taken independently among th group comprising hydrogen atom, halogen atom, hydroxyl, alkyl, alkoxy-group, -CF3, amino-group, -NHC(O)N(C1-C3-alkyl)-C(O)NH-(C1-C3-alkyl), -NHC(O)NH-(C1-C6-alkyl), alkylamino-, alkoxyalkoxy-group, aryl, aryloxy-, arylamino-group, heterocyclyl, heterocyclylalkyl, heterocyclylamino-group wherein heteroatom is taken among N atom or O atom, -NHSO2-(C1-C3-alkyl), aryloxyalkyl; R4 is taken among the group comprising hydrogen atom, aryl, aralkyl, benzofuranyl, dihydrobenzofuranyl, dihydroindenyl, alkyl, benzodioxolyl, dihydrobenzodioxynyl, furyl, naphthyl, quinolinyl, isoquinolinyl, pyridinyl, indolyl, thienyl, biphenyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, pyrimidinyl and carbazolyl. Other values of radicals are given in the claimed invention. Also, invention relates to pharmaceutical composition used for inhibition binding α4β1-integrin in mammal based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for treatment or prophylaxis of diseases associated with α4β1-integrin.

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

33 cl, 7 tbl, 42 ex

Indole derivatives // 2256659

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

SUBSTANCE: invention relates to new derivatives of indole of the formula (I): wherein R1 means phenyl substituted or unsubstituted radical R2 and/or R4; R2, R4 R5 and R6 in each case and independently of one another mean Hal; R3 mean substituted or unsubstituted radical R5 and/or R6 or means Het wherein Het means 2-furyl, 3-furyl, 2-thienyl or 3-thienyl; Hal means fluorine atom (F), chlorine atom (Cl), bromine atom (Br) or iodine atom (J), and their physiologically acceptable salts and solvates also. Compounds of the formula (I) are prepared by interaction of compound of the formula (I): wherein L means Cl, Br, J or free or reactive functional modified group OH; R3 has value indicated in the formula (I) with compound of the formula (III): . Compounds of the formula (I) show affinity to 5-HT2A receptors that allow their using in the pharmaceutical composition.

EFFECT: valuable medicinal and pharmacological properties of compounds.

4 cl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of tetrahydroisoquinoline of the formula [I] wherein R1 represents hydrogen atom or lower alkyl; R2 represents alkyl having optionally a substitute taken among alkoxycarbonyl and carboxy-group, cycloalkyl, cycloalkylalkyl, aryl having optionally a substitute taken among lower alkyl, arylalkyl having optionally a substitute taken among lower alkyl, lower alkoxy-group, halogen atom and acyl, alkenyl, alkynyl, or monocyclic heterocyclylalkyl wherein indicated heterocycle comprises 5- or 6-membered ring comprising nitrogen atom and having optionally a substitute taken among lower alkyl; R3 represents hydrogen atom or lower alkoxy-group; A represents a direct bond or >N-R5 wherein R5 represents lower alkyl; B represents lower alkylene; Y represents aryl or monocyclic or condensed heterocyclyl comprising at least one heteroatom taken among oxygen atom and nitrogen atom and having optionally a substitute taken among lower alkyl, carboxy-group, aryl, alkenyl, cycloalkyl and thienyl, or to its pharmaceutically acceptable salt. Also, invention relates to pharmaceutical composition eliciting hypoglycaemic and hypolipidemic effect based on these derivatives. Invention provides preparing new compounds and pharmaceutical agents based on thereof, namely, hypoglycaemic agent, hypolipidemic agent, an agent enhancing resistance to insulin, therapeutic agent used for treatment of diabetes mellitus, therapeutic agent against diabetic complication, agent enhancing the tolerance to glucose, agent against atherosclerosis, agent against obesity, an anti-inflammatory agent, agent for prophylaxis and treatment of PPAR-mediated diseases and agent used for prophylaxis and treatment of X-syndrome.

EFFECT: valuable medicinal properties of compounds and composition.

13 cl, 7 tbl, 75 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new piperidine compounds of the general formula (I) wherein A means preferably ring of the formula:

wherein R1 means hydrogen atom (H), cyano-group (CN), (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkenyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group; W means (C1-C6)-alkylene that can be substituted, ordinary bond; Z means optionally substituted aromatic hydrocarbon cyclic (C6-C14)-group; l means a number from 0 to 6. Compounds show the excellent activity directed for inhibition of sodium channels and selective inhibition of potassium channels.

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

26 cl, 4 tbl, 476 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to applying compounds of the general formula (1):

as inhibitors of caspase-3 that allows their applying as "molecular tools" and as active medicinal substances inhibiting selectively the scheduling cellular death (apoptosis). Also, invention relates to pharmaceutical compositions based on compounds of the formula (1), to a method for their preparing and a method for treatment or prophylaxis of diseases associated with enhanced activation of apoptosis. Also, invention relates to new groups of compounds of the formula 91), in particular, to compounds of the formulae (1.1):

and (1.2):

. In indicated structural formulae R1 represents inert substitute; R2, R3 and R4 represent independently of one another hydrogen atom, fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J). CF3, inert substitute, nitro-group (NO2), CN, COOH, optionally substituted sulfamoyl group, optionally substituted carbamide group, optionally substituted carboxy-(C1-C6)-alkyl group; R5 represents oxygen atom or carbon atom included in optionally condensed, optionally substituted and optionally comprising one or some heteroatoms; R6 represents hydrogen atom or inert substitute; X represents sulfur atom or oxygen atom.

EFFECT: improved preparing and applying methods, valuable medicinal and biochemical properties of compounds.

3 cl, 1 dwg, 2 tbl, 1 sch, 8 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: present invention relates to new 4-piperazinyl-(8-quinolinyl)-methyl)-benzamides of general formula I

1, wherein R1 is phenyl, pyridinyl, thiophenyl, furanyl, and inidazolyl, and each phenyl or heteroaromatic ring is optionally and independently substituted with 1, 2 or 3 substituents, selected from linear or branched C1-C6-alkyl, NO2, CF3, C1-C6-alkoxy, halogen, or pharmaceutically acceptable salts thereof. Compounds of present invention are useful in therapy, in particular for pain alleviation. Also disclosed are pharmaceutical composition based on compounds of formula I and method for pain treatment.

EFFECT: new compounds and compositions for pain treatment.

12 ck, 19 ex, 3 tbl

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