Modulators of alpha 7 nicotinic acetylcholine receptors alpha 7 and their therapeutic applications

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of general formula (I) and its pharmaceutically acceptable salts. In general formula (I) , Y represents group -CONH(Q)- or -NHCONH(Q)-; Q represents 6-member aromatic ring or 5-10-member heteroaromatic ring, containing one or two N heteroatoms or two O heteroatoms; R represents hydrogen, halogen, linear or branched (C1-C6)alkyl; (C1-C6)alkoxy; di-(C1-C6)alkylamino, 5-member heteroaromatic ring, containing one O or S heteroatom; 6- or 9-member heteroaromatic ring, containing one or two N heteroatoms; phenyl, mono- or disubstituted with halogen, (C1-C6)alkyl, halogeno(C1-C6)alkyl, (C1-C6)alkoxy, acyl; hydroxy; piano; di-(C1-C6)alkylamino, acylamino' carbamoyl; X represents group : where Z represents CH2, N or O; m represents integer number from 1 to 3; p is equal 0, 1; R" is selected from group, consisting of di-( C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl. Invention also relates to pharmaceutical composition, containing as active ingredient, invention compound, to application of invention compound for manufacturing pharmaceutical composition, to method of inhibition of nicotinic acetylcholine receptor α7.

EFFECT: obtaining compound, which possesses agonistic activity with respect to nicotinic acetylcholine receptor (nAChR) α7.

7 cl, 2 tbl, 4 dwg, 270 ex

 

The text descriptions are given in facsimile form.

1. The compound of General formula (I)

where Y represents a group-CONH(Q) -, or-NHCONH(Q)-;
Q is a 6-membered aromatic ring or 5-10-membered heteroaromatic ring containing one or two heteroatom N or two heteroatoms About;
R represents hydrogen; halogen; linear or branched (C1-C6)alkyl, (C1-C6)alkoxy; di-(C1-C6)alkylamino, 5-membered heteroaromatic ring containing one heteroatom O or S; a 6 - or 9-membered heteroaromatic ring containing one or two heteroatoms N; phenyl, mono - or disubstituted by halogen; and (C1-C6)alkyl, halogeno(C1-C6)alkyl, (C1-C6)alkoxy, acyl; hydroxy; cyano; CI-(C1-C6)alkylamino, acylamino; carbamoyl;
X represents a group

where Z represents CH2, N or O;
m is an integer from 1 to 3;
p is 0, 1;
R" is selected from the group consisting of di-(C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl,
and its pharmaceutically acceptable salts,
with the exception of the following compounds:
N-[4-(dimethylamino)phenyl]-1-piperidineacetate,
N-(4-acetylphenyl)-1-piperidineacetate,
N-(4-methoxyphenyl)-1-piperidineacetate,
N-phenyl-1-Pipa is identitymine,
N-(4-were)-1-piperidineacetate,
N-(4-chlorophenyl)-1-piperidineacetic.

2. The compound according to claim 1, where
Y represents-CONH(Q)-;
Q is a 6-membered aromatic ring or 5-10-membered heteroaromatic ring containing one or two heteroatom N or two heteroatoms About;
R is selected from the group consisting of phenyl; pyridyl; pyrimidinyl; indolyl; tanila; furanyl; benzoimidazolyl, possibly substituted as indicated in claim 1;
X represents a group

where Z represents CH2, N or O;
m is an integer from 1 to 3;
p is 0, 1;
R" is selected from the group consisting of di-(C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl.

3. The compound according to claim 1, where
Y represents a-NHCONH(Q)-;
Q is a 6-membered aromatic ring or 5-10-membered heteroaromatic ring containing one or two heteroatom N or two heteroatoms About;
R is selected from the group consisting of halogen; linear or branched (C1-C6)alkyl, (C1-C6)alkoxy, di(C1-C6)alkylamino; phenyl; pyridyl; pyrimidinyl; indolyl; tanila; furanyl; benzoimidazolyl, possibly substituted as indicated in claim 1;
X represents a group

where Z represents CH 2, N or O;
m is an integer from 1 to 3;
p is 0, 1;
R" is selected from di-(C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl.

4. Pharmaceutical composition having agonistic activity against nicotinic acetylcholine receptor α7 containing as active ingredient a compound according to any one of claims 1 to 3 in combination with a pharmaceutically acceptable carrier or excipient.

5. The use of compounds according to any one of claims 1 to 3 for the manufacture of a pharmaceutical composition having agonistic activity against nicotinic acetylcholine receptor α7.

6. The use according to claim 5 to obtain a pharmaceutical composition for the treatment of Alzheimer's disease.

7. The method of inhibition of nicotinic acetylcholine receptor (nAChR) alpha 7, comprising introducing an effective amount of a compound according to any one of claims 1 to 3.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel heterocyclic compounds of formula (1) , where ring Q represented by is , (where is NH-CH2-, -N-CH-, -CH2-NH- or -CH=N-; and the carbon-carbon bond between the 3rd position and the 4th position of the heterocyclic skeleton which contains Z and Y, is a single or double bond); ring Q can have at least one substitute selected from a group consisting of a lower alkyl group, lower alkenyl group, lower alkynyl group, hydroxy group, lower alkoxy group, halogenated lower alkyl group, aryl group, aryl lower alkyl group, aryl lower alkoxy group, arylcarbonyl group, lower alkenyloxy group, lower alkanoyl group, lower alkanoyloxy group, cycloalkyl group, cycloalkyl lower alkyl group, halogen atom, carbamoyl group which can have a lower alkyl group, carboxy group, lower alkoxycarbonyl group, amino group which can have a lower alkanoyl group, nitro group, hydroxy lower alkyl group, amino lower alkyl group which can have a lower alkyl group, thienyl group, lower alkyl group substituted with a saturated 3-8-member monoheterocyclic group containing 1-2 nitrogen atoms, and an oxo group; R2 is a hydrogen atom or a lower alkyl group; and A is -O-A1- (where A1 is an alkylene group which can be substituted with a hydroxy group (where the alkylene group may contain one oxygen atom) or a lower alkenylene group or a lower alkylene group; provided that if A is a lower alkylene group, Q is a bicyclic group selected from a group consisting of: (where the carbon-carbon bond is a single or double bond)] or salts thereof. The invention also relates to a pharmaceutical composition, to a method of preparing the pharmaceutical composition, to use of the formula (1) heterocyclic compound, as well as a method for synthesis of the heterocyclic compound.

EFFECT: obtaining novel biologically active compounds which have activity as a dopamine D2 receptor partial agonist and a serotonin receptor 5-HT2A antagonist, and an adrenaline receptor α1 antagonist, and serotonin uptake inhibitor or serotonin reuptake inhibitor.

15 cl, 197 ex, 24 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: in formula (1) A is a nitrogen atom or CH; when A is a nitrogen atom, B is NR9 (where R9 is a C1-10alkyl group), when A is CH, B is a sulphur atom, R1 is a phenyl group (where the phenyl group is substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-10alkyl group and C1-10alkoxy groups (where C1-10alkyl groups and C1-10alkoxy groups are not substituted of substituted with one or more halogen atoms)); L1 is a bond; X is OH; R2 is a C1-6alkyl group; L2 is a bond; L3 is NH; L4 is a bond or NH; Y is an oxygen atom or sulphur atom; R3 is a thienyl group (where the thienyl group is substituted with CONR29R30 (where R29 is hydrogen or a C1-10alkyl group, and R30 is an amino group (where the amino group is not substituted or substituted with a pyridyl group), mono- or di-C1-10alkylamino group, N-methylpiperzinyl group, piperidine group, morpholine group or C1-10alkyl group (C1-10alkyl group is substituted with one or more substitutes selected from a group consisting of a carboxyl group, carbamoyl groups, pyrroldinyl groups, tetrahydrofuryl groups or morpholine groups) or R29 and R30 together denote -(CH2)m3-G-(CH2)m4- (where G is CR31R32 (where R31 is a hydrogen atom and R32 is a C1-10alkylcarbonylamino group or pyrrolidinyl group) and each of m3 and m4 is independently equal to an integer from 0 to 5 provided that m3+m4 equals 3, 4 or 5), or NR29R30 as a whole denotes a piperidine group or pyrrolidinyl group (where the piperidine group or pyrrolidinyl group is substituted with two substitutes independently selected from a group consisting of: hydroxyl groups and C1-10alkoxy groups) or 2-(4-oxopyrridin-1(4H)-yl)acetyl group), phenyl group (where the phenyl group is substituted with one substitute selected from a group consisting of C1-10alkyl groups, C1-10alkylcarbonyl groups and C1-10alkylaminocarbonyl groups, (where C1-10alkyl group, C1-10alkylcarbonyl group and C1-10alkylaminocarbonyl group are substituted with one or two substitutes selected from a group consisting of hydroxyl groups, carboxyl groups and carbamoyl groups)), phenyl group (where the phenyl group is substituted with one C1-10alkylaminocarbonyl group or one halogen atom), dihydrobenzo[1,4]dioxine group or benzo[1,4]oxazine group. The invention also relates to a medicinal agent containing the disclosed compound as an active ingredient and to a thromopoeitin receptor activator which is a formula (1) compound.

EFFECT: disclosed compounds have thrombopoietin receptor agonist properties.

8 cl, 11 tbl, 128 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for preparing 1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)azetidine-3-ol or its salts which involves the use as a parent compound, (phenylthio)acetic acid derivative or its salts presented by general formula: where X1 represents halogen atom, and is applicable as a safe method of volume production of 1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)azetidine-3-ol or its salts effective as an agent in disorders of the central nervous system and peripheral nervous system.

EFFECT: there is provided high yield, safety for human body, low environment loads.

36 cl, 1 tbl, 33 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (II) and to their pharmaceutically acceptable salts. In formula R1 means phenyl optionally substituted on one or more carbon atoms with one or more R9; where R9 is specified of halogen, amino, C1-6alkyl and C1-6alkoxy, one of R2 and R3 represents -C(=O)NR6R7, and the other represents -NHC(=O)NHR4; R4 and R6 represent N, and R7 represents piperidine-3-yl. Besides the invention refers to a pharmaceutical composition containing the compound of the invention, to application of the compound for preparing a drug, and also to an intermediate compound of formula (XI) or its salts, where A represents thienyl ring.

EFFECT: preparation of new compounds exhibiting inhibitory properties with respect to SNK1 kinase.

7 cl, 263 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula (1) , where substitutes are as defined in paragraph 1 of the invention. The compounds have fungicide properties. The method of obtaining formula (1) compounds is described, in which n equals 0. Described also is a fungicide composition based on formula (1) compounds and a phytopathogenic fungus control method which uses compounds in paragraph 1 or a composition based on the said compounds.

EFFECT: obtaining novel compounds which can be used as fungicides.

24 cl, 312 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1), their tautomers and pharmaceutically acceptable salts. The disclosed compounds have thromobopoietin receptor agonist properties. In formula (1) , A is a nitrogen atom or CH, when A is a nitrogen atom, B is NR9 (where R9 is a C1-10 alkyl group), and when A is CH, B is a sulphur atom, R1 is a phenyl group (the phenyl group is substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-10 alkyl groups and C1-10 alkoxy groups (C1-10 alkyl groups and C1-10 alkoxy groups are unsubstituted or substituted with one or more halogen atoms)), L1 is bond, X is OH, R2 is a C1-10 alkyl group, L2 is a bond, L3 is NH, L4 is a bond or NH, Y is a sulphur atom, and when L4 is a bond, R3 is a piperidinyl group, a piperazinyl group (the piperidinyl group and the piperazinyl group are substituted with substitutes selected from a group containing C1-10 alkoxycarbonyl groups, carboxyl group, hydroxyl groups, di-C1-10 alkylaminocarbonyl groups, C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups (C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups are substituted with a substitute selected from a group containing pyridyl groups, hydroxyl groups and carboxyl groups)), or when L4 is NH, R3 is a C1-10 alkyl group (C1-10 alkyl group is substituted with a substitute selected from a group containing C1-10 alkoxy groups, C1-10 alkoxycarbonyl groups or carboxyl groups).

EFFECT: obtaining a thrombopoietin receptor activator which is a formula (1) compound and a medicinal agent which contains the disclosed compound as an active ingredient.

10 cl, 3 tbl, 47 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline, represented by formula , where R1 represents (1-6C)alkyl; R2 represents halogen, (1-4C)alcoxy; R3 represents OH, NO2, CN, fluoridated with (1-4C)alkoxy, (1-4C)alkoxy(2-4C)alkoxy. hydroxy(2-4C)alkoxy, (1-4C)alkoxycarbonyl, R7, R8-amino, R9, R10-amino, R9, R10-aminocarbonyl, R9, R10-aminosulfonyl or phenyl(1-4C)alkoxy, where phenyl ring in composition phenyl(1-4C)alkoxy is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R4 represents R11-phenyl or R11-(4-5C)heteroaryl, which represents heteroaromatic group, containing 4-5 carbon atoms and at least one heteroatom, selected from N and S, where phenyl or heteroaryl group is optionally additionally substituted with one or several substituents, selected from nitro, (1-4C)alkyl, (1-4C)alkoxy; R7 represents H, (1-4C)alkyl; R8 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy(1-4C)alkylcarbonyl, furylcarbonyl; phenyl(1-4C)alkylcarbonyl, where phenyl ring is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R9 and R10 are not necessarily selected from H, (1-6C)alkyl and (1-4C)alkoxy(2-4C)alkyl; or R9 and R10 can be bound together with formation of morpholinyl ring; R11 represents H, R12, R13-amino, R14, R15-aminocarbonyl or R14, R15-aminosulfonyl; R12 represents H; R13 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyperazinyl(1-4C)alkylcarbonyl; R14 and R15 are independently selected from H, (1-6C)alkyl, (1-4C)alkoxy(2-4C)alkyl and imidazolyl(1-4C)alkyl; X represents O or R16-N; Y represents CH2 or C(O);Z represents CN; R16 represents H, (1-4C)alkyl, (1-4C)alkylcarbonyl; or their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives by any of i.i. 1-10.

EFFECT: obtaining novel biologically active compounds, which possess agonistic activity with respect to FSH receptor.

13 cl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention describes an amide of formula:

where A and B are independently selected from CH or N; D is H; Z is selected from hydrogen, unsubstituted C1-8alkyl, each L is independently selected from -CraRb-, -CRa=, -CO-, -O- or -NRa-; k, m, n, q, x and w are integers independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, provided that k+m+n+q+x+w equals at least 4; R1-R6 are independently selected from hydrogen, CN or halogen; Ra and Rb are independently selected from hydrogen, unsubstituted C1-8alkyl, or its pharmaceutically acceptable salt. The invention describes a pharmaceutical composition, use of the compounds to treat AChE-mediated diseases, a treatment method, as well as an amide synthesis method and use of the formula (I) amide as a chemical agent for inhibiting acetylcholinesterase in biological research.

EFFECT: compounds have high acetylcholinesterase or butyrylcholinesterase inhibiting activity.

24 cl, 27 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: in embodiments of the invention, specific compounds are used to prepare a medicinal agent for treating, relieving and preventing conditions associated with dysfunction of monoamine transmission. The compounds have general formula (1) , where: R1 and R2 are identical or different and denote hydrogen, alkyl, alkenyl, alkynyl, aryl, thio or alkylthio, or R1 and R2 may have extra substitutes which are selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkyloxy, morpholin-4-ylalkoxy, piperidin-1-ylalkyloxy, alkylamino, dialkylamino, arylamino.

EFFECT: more efficient use of compounds in preparing medicinal agents.

8 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of substituted 4-(benzimidazol-2-ylmethylamino)benzamidine of formula (I) or its physiologically compatible salt, in which R1 is a C1-C3alkyl group, R2 is a R21NR22 group, where R21 denotes a C1-C3alkyl group substituted with a C1-C3alkoxycarbonyl group, and R22 denotes a pyridinyl group, and R3 is a C1-C8alkoxycarbonyl group having thrombin inhibiting and thrombin clotting time prolonging activity. The method involves a step (a) where phenyldiamine of formula (II) in which R1 and R2 assume values given for formula (I), reacts with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid. At step (b), the obtained product of formula (III), in which R1 and R2 assume values given for formula (I), is hydrogenated and then at step (c), if necessary, the obtained product of formula (I), in which R3 is hydrogen, reacts with a compound of formula R3-X (IV), in which R3 assumes values given for formula (I), and X denotes an acceptable leaving group, and then converted to a physiologically compatible salt if necessary. The invention also relates to novel intermediate products - formula (III) compound, in which R1 and R2 assume values given for formula (I), as well as to 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid, 4-(1,2,4-oxadiazol-5-on-3-yl)aniline and toluene sulphonate N-(2-pyridinyl)-N-(2-ethoxycarbonylethyl)amide 1-methyl-2-[N-[4-amidinophenyl]aminomethyl]benzimidazol-5-yl carboxylic acid.

EFFECT: agents are highly effective.

12 cl, 2 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives having FAK inhibitory activity of formula (I), where R0 is hydrogen; R1 is a 5- or 6-member heterocycle containing 1 or 2 nitrogen atoms substituted with (C1-C7)alkyl, hydroxyl group, dialkylamino group or a 6-member heterocycle containing one nitrogen atom; R2 is hydrogen; R3 is carbamoyl substituted once or twice with (C1-C7)alkyl; a 5-member heterocycle containing 4 nitrogen atoms; SO2N(R12)R13, where R12 is hydrogen or (lower)alkyl, and R13 is hydrogen, (C1-C7)alkyl, (C1-C7)alkoxy(C1-C7)alkyl, di(C1-C7)alkylamino(C1-C7)alkyl, hydroxy(C1-C7)alkyl, or R12 and R13 together a nitrogen atom with which they are bonded form a 6-member heterocycle containing two nitrogen atoms, where the said heterocycle is not substituted or substituted with (C1-C7)alkyl; R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; (C1-C7)alkoxy; carbamoyl which is not substituted or substituted with (lower)alkyl; a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with di(C1-C7)alkylamino, (C1-C7)alkyl, hydroxy, 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms, unsubstituted or substituted with (C1-C7)alkyl; 6-member heterocycle-oxy containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms which is not substituted or substituted with (C1-C7)alkyl; R8 is hydrogen; halide; (C1-C7)alkoxy, carbamoyl unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5-member heterocycle containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with one or two substitutes independently selected from hydroxy, (C1-C7)alkyl, aminocarbonyl and (C1-C7)alkylamino; 6-member heterocycle-oxy, containing 1 nitrogen ring atom, unsubstituted or substituted 1-5 times with (C1-C7)alkyl or di(C1-C7)alkylamino; or R7 and R8 together with atoms with which they are bonded form a 6-member heterocycle containing two nitrogen or oxygen atoms, unsubstituted or substituted once or twice with (C1-C7)alkyl or oxo group; R9 is hydrogen; R10 is (C1-C7)alkoxy, as well as to their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and synthesis method.

EFFECT: novel compounds have useful biological activity.

4 cl, 167 ex

FIELD: medicine.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (I) or their pharmaceutically acceptable salts which possess inhibiting activity with respect to focal adhesion kinase (FAK), proteintyrosinekinase ZAP-70, receptor of insulin-like growth factor 1 (IGF-1R), tyrosinekinase activity of anaplastic lymphoma (ALK) and fusion protein NPM-ALK. In formula (I) , R0, R1 and R2 independently represent hydrogen, C1-C8 alkyl, 5- or 6-member heterocycle, containing 1,2 or 3 heteroatoms, selected from N, O and S, C1-C8alkoxy group, C1-C8alkylsulphinyl, C1-C8alkylsulphonyl, C5-C10arylsulphonyl, halogen, carbamoyl, sulphamoyl, etc.; R3 represents C1-C8alkylsulphinyl, C1-C8alkylsulphonyl, C5-C10arylsulphonyl, carbamoyl or sulphamoyl; R4 represents hydrogen or C1-C8alkyl; R5 represents chlorine or bromine; R6 represents hydrogen; R7, R8, R9 and R10 independently represent C1-C8alkyl, C5-C10aryl, possibly substituted by 5- or 6-member heterocycle, containing 1, 2 or 3 heteroatoms, selected from N, O and S, where substituents are selected from C1-C8alkyl, hydroxy, hydroxy-C1-C8alkyl, C1-C8alkoxy C1-C8alkyl, cyano, oxo, C1-C8alkylamino, diC1-C8alkylamino, carbamoyl, C1-C8alkylcaronyl, 5-10-member heterocycle, containing 1, 2 or 3 heteroatoms, selected from N and O, which is probably substituted by C1-C8alkyl; C1-C8alkoxy group, halogen- C1-C8alkoxy group, etc; A represents C. Invention also relates to pharmaceutical composition and to application of compounds of formula (I) for preparation of medication.

EFFECT: novel compounds possess useful biologic activity.

15 cl, 61 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-substituted derivatives of oxamic acid thiohydrazides of general formula: , where R and R1 denote H, unsubstituted or substituted Het, phenyl, Alk, wherein substitutes can be Alk, Hal, CF3, COOR3, SR3, or R+R1=C2H4OC2H4; R2 denotes H, Alk, OR3, Hal, where R3=Alk; Het denotes a 5- or 6-member ring which contains one or two heteroatoms selected from N and S. The invention also relates to a method for synthesis of said compounds.

EFFECT: obtaining novel compounds which exhibit antibacterial activity and can be used as antibacterial agents for inhibiting pathogenic bacteria, including Chlamydia.

4 cl, 21 ex

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