Novel amide derivative and use thereof as medicinal agent

FIELD: chemistry.

SUBSTANCE: invention relates to an amide derivative of formula (I), where A is benzene or pyridine, where the benzene or pyridine optionally contain 1 or 2 or 3 identical or different substitutes selected from an alkyl containing 1-6 carbon atoms, a cycloalkyl containing 3-6 carbon atoms, an alkoxy containing 1-6 carbon atoms, a halogen atom, nitro, cyano, alkylsulphonyl containing1-6 carbon atoms, amino, cyclic amine selected from 1,1-di-oxoisothiazolidinyl, 2-oxooxazolidinyl, oxopyrrolidinyl, 1,1-dioxothiazinyl and 2-oxoimidazolidinyl optionally having a substitute selected from an alkyl containing 1-6 carbon atoms and an alkylcarbonyl containing a total of 2-7 carbon atoms, acylamino containing a total of 2-7 carbon atoms, and an alkylsulphonyl amino containing 1-6 carbon atoms, wherein the right-side bond is linked to the carbonyl and the left-side bond is linked to the nitrogen atom, R1 and R2 are identical or different and each is a hydrogen, an alkyl containing 1-6 carbon atoms and optionally containing 3 halogen atoms as substitutes, a cycloalkyl containing 3-6 carbon atoms, a phenyl, a halogen atom or a cyano group and R1 and R2 are not a hydrogen atom at the same time, R3 is a hydrogen atom, an alkyl containing 1-6 carbon atoms, an alkenyl containing 2-6 carbon atoms, a cycloalkyl containing 3-6 carbon atoms, or a halogen, R4a, R4b and R4c are each independently a hydrogen atom, an alkyl containing 1-6 carbon atoms, or an oxo, R5a, R5b and R5c are identical or different and each is a hydrogen atom, an alkyl containing 1-6 carbon atoms and optionally containing substitute(s) selected from phenyl, an alkoxy group containing 1-6 carbon atoms, optionally substituted with an alkoxy group containing 1-6 carbon atoms, a phyenylcarbonyloxy group and a hydroxy group, or a phenyl, X is a carbon atom (any of R4a, R4b and R4c can be bonded to a carbon atom, but the carbon atom is not substituted with oxo) or a nitrogen atom (if Y is a single bond, the nitrogen atom can be oxidised to form an N oxide), Y is a single bond, a carbonyl or an oxygen atom, Z1 and Z2 are each independently a carbon atom (substitute R3 is optionally bonded to a carbon atom) or a nitrogen atom, and m equals 1 or 2, a pharmacologically acceptable salt thereof. The amide derivative is used as a preventive/therapeutic drug for treating autoimmune diseases, inflammatory bowel diseases or osteoarthritis.

EFFECT: amide derivative which suppresses production of inductive type MMP-9.

14 cl, 4 tbl, 581 ex

 

The text descriptions are given in facsimile form.

1. Amide derivative represented by the following formula (I)

where a represents a group of the following formula
oror
where the benzene and pyridine optionally contain 1, or 2, or 3 identical or different substituent selected from alkyl containing 1-6 carbon atoms, cycloalkyl containing 3-6 carbon atoms, alkoxy containing 1-6 carbon atoms, halogen atom, nitro, cyano, alkylsulfonyl containing 1-6 carbon atoms, amino, cyclic amine selected from 1,1-di-oxoazetidin, 2-oxoacridine, oxopyrrolidin, 1,1-dioxothiazolidine and 2-Oxymetazoline, which optionally has a Deputy selected from alkyl containing 1-6 carbon atoms, and alkylcarboxylic containing the total number of 2-7 carbon atoms, acylamino containing the full number of 2-7 carbon atoms, and alkylsulfonyl containing 1-6 carbon atoms, with the right communication associated with the carbonyl and the left link is connected to the nitrogen atom,
R1and R2the same or different and each represents a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing 3 halogen atom as a substituent, cycloalkyl containing 3-6 carbon atoms, phenyl, halogen atom or cyano group, and R1and R2at the same time do not represent a hydrogen atom,
R3represents a hydrogen atom, alkyl containing 1-6 carbon atoms, alkenyl containing 2-6 carbon atoms, cycloalkyl containing 3-6 and the Ohm carbon, or halogen,
R4a, R4band R4ceach independently represents a hydrogen atom, alkyl containing 1-6 carbon atoms or oxo,
R5a, R5band R5cthe same or different and each represents a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing substituent(s)selected from phenyl, alkoxygroup containing 1-6 carbon atoms, optionally substituted by alkoxygroup containing 1-6 carbon atoms, phenylcarbonylamino and hydroxy-group, or phenyl,
X represents a carbon atom (any of the R4a, R4band R4cmay be associated with an atom of carbon, but the carbon atom is not substituted by oxo) or nitrogen atom (if Y represents a simple bond, the nitrogen atom may be oxidized with the formation of N-oxide),
Y represents a simple bond, carbonyl or oxygen atom,
Z1and Z2each independently represents a carbon atom (the substituent R3not necessarily associated with carbon atom or a nitrogen atom, and m represents 1 or 2,
its pharmacologically acceptable salt.

2. Amide derivative according to claim 1, where a represents a group of the following formula

where benzene optionally contains 1 or 2 or 3 identical or different substituent selected from alkyl containing 1-6 of atomo the carbon cycloalkyl containing 3-6 carbon atoms, alkoxy containing 1-6 carbon atoms, halogen atom, nitro, cyano, alkylsulfonyl containing 1-6 carbon atoms, amino, cyclic amine selected from 1,1-di-oxoazetidin, 2-oxoacridine, oxopyrrolidin, 1,1-dioxothiazolidine and 2-Oxymetazoline, which optionally has a Deputy selected from alkyl containing 1-6 carbon atoms, and alkylcarboxylic containing the full number of 2-7 carbon atoms, acylamino containing the full number of 2-7 carbon atoms, alkylsulfonyl containing 1-6 carbon atoms, with the right communication associated with carbonyl and the left link is connected to the nitrogen atom, its pharmaceutically acceptable salt.

3. Amide derivative according to claim 1, where a represents a group of the following formula
or
where pyridine optionally contains 1 or 2 or 3 identical or different substituent selected from alkyl containing 1-6 carbon atoms, cycloalkyl containing 3-6 carbon atoms, alkoxy containing 1-6 carbon atoms, halogen atom, nitro, cyano, alkylsulfonyl containing 1-6 carbon atoms, amino, cyclic amine selected from 1,1-di-oxoazetidin, 2-oxoacridine, oxopyrrolidin, 1,1-dioxothiazolidine and 2-Oxymetazoline, which is th is optional Deputy, selected from alkyl containing 1-6 carbon atoms, and alkylcarboxylic containing the full number of 2-7 carbon atoms, acylamino containing the full number of 2-7 carbon atoms, alkylsulfonyl containing 1-6 carbon atoms, with the right communication associated with the carbonyl and the left link is connected to the nitrogen atom, its pharmaceutically acceptable salt.

4. Amide derivative according to claim 1, where the benzene and pyridine And for optionally contain 1, or 2, or 3 identical or different substituent selected from alkyl containing 1-6 carbon atoms, cycloalkyl containing 3-6 carbon atoms, alkoxy containing 1-6 carbon atoms, halogen atom, nitro, cyano, alkylsulfonyl containing 1-6 carbon atoms, amino, cyclic amine selected from 1,1-dioxothiazolidine, 2-oxoacridine, oxopyrrolidin, 1,1-dioxothiazolidine and 2-Oxymetazoline, which optionally has a Deputy selected from alkyl containing 1-6 carbon atoms and alkylcarboxylic containing the full number of 2-7 carbon atoms, acylamino containing the full number of 2-7 carbon atoms, and alkylsulfonyl containing 1-6 carbon atoms, or its pharmacologically acceptable salt.

5. Amide derivative according to claim 1, where X represents a carbon atom (any of the R4a, R4band R4ccan be linked to a carbon atom, but complered not substituted by oxo), or its pharmacologically acceptable salt.

6. Amide derivative according to claim 1, where R1and R2the same or different and each represents a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing 3 halogen atom as a substituent, cycloalkyl containing 3-6 carbon atoms, halogen atom or cyano, where R1and R2at the same time do not represent hydrogen atoms,
R3represents a hydrogen atom, alkyl containing 1-6 carbon atoms, alkenyl containing 2-6 carbon atoms, cycloalkyl containing 3-6 carbon atoms or a halogen atom,
R4a, R4band R4ceach independently represents a hydrogen atom or alkyl containing 1-6 carbon atoms,
R5a, R5b, R5cthe same or different and represent a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing substituent(s)selected from phenyl, alkoxygroup containing 1-6 carbon atoms, optionally substituted by alkoxygroup containing 1-6 carbon atoms, phenylcarbonylamino and hydroxy-group, or phenyl,
X represents a carbon atom (any of the R4a, R4band R4cmay be associated with an atom of carbon, but the carbon atom is not substituted by oxo),
Y represents a carbonyl or oxygen atom,
Z1and Z2what each represents a carbon atom (the substituent R 3not necessarily associated with carbon atom), and
m represents 1,
or its pharmacologically acceptable salt.

7. Amide derivative according to claim 1, where X represents a nitrogen atom (the nitrogen atom may be oxidized with the formation of N-oxide) or its pharmacologically acceptable salt.

8. Amide derivative according to claim 1, where R1and R2the same or different and each represents a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing 3 halogen atom as a substituent, cycloalkyl containing 3-6 carbon atoms, halogen atom or cyano, where R1and R2at the same time do not represent hydrogen atoms,
R3represents a hydrogen atom, alkyl containing 1-6 carbon atoms, alkenyl containing 2-6 carbon atoms, cycloalkyl containing 3-6 carbon atoms or a halogen atom, R4a, R4band R4ceach independently represents a hydrogen atom, alkyl containing 1-6 carbon atoms or oxo,
R5a, R5band R5cthe same or different and represent a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing substituent(s)selected from phenyl, alkoxygroup containing 1-6 carbon atoms, optionally substituted by alkoxygroup containing 1-6 carbon atoms, phenylcarbonylamino and hydro is syrupy, or phenyl,
X represents a nitrogen atom (the nitrogen atom may be oxidized with the formation of N-oxide),
Y represents a simple bond,
Z1and Z2each independently represents a carbon atom (the substituent R3not necessarily associated with carbon atom or a nitrogen atom, and
m represents 1 or 2, or
its pharmacologically acceptable salt.

9. Amide derivative according to claim 1, where R1and R2the same or different and each represents alkyl containing 1-6 carbon atoms and optionally containing 3 halogen as a substituent, cycloalkyl containing 3-6 carbon atoms, halogen atom or cyano,
R3represents a hydrogen atom, alkyl containing 1-6 carbon atoms, cycloalkyl containing 3-6 carbon atoms or a halogen atom,
R4a, R4band R4ceach independently represents a hydrogen atom or alkyl containing 1-6 carbon atoms,
R5a, R5band R5cthe same or different and each represents a hydrogen atom, alkyl containing 1-6 carbon atoms and optionally containing substituent(s)selected from phenyl, alkoxygroup containing 1-6 carbon atoms, optionally substituted by alkoxygroup containing 1-6 carbon atoms, phenylcarbonylamino and hydroxy-group, or phenyl,
X represents the volume of nitrogen (the nitrogen atom may be oxidized with the formation of N-oxide),
Y represents a simple bond,
Z1and Z2each independently represents a carbon atom (the substituent R3not necessarily associated with carbon atom or a nitrogen atom, and
m represents 1 or 2, or
its pharmacologically acceptable salt.

10. The agent for suppressing the production of MMP-9, comprising the amide derivative according to any one of claims 1 to 9, its pharmacologically acceptable salt.

11. Agent for prevention and/or treatment of autoimmune disease or inflammatory bowel disease, comprising the amide derivative according to any one of claims 1 to 9, or its pharmacologically acceptable salt.

12. The agent according to claim 11, where the autoimmune disease is rheumatoid arthritis, multiple sclerosis or systemic lupus erythematosus.

13. The agent according to claim 11, where the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

14. Agent for prevention and/or treatment of osteoarthritis, comprising the amide derivative according to any one of claims 1 to 9, or its pharmacologically acceptable salt.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: application describes prodrugs being 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitryl derivatives, and a method for preparing them.

EFFECT: invention can find application in treating and/or preventing cardiovascular diseases.

8 cl, 4 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to isoxazole-pyridine derivatives of formula , where X; R1; R2, R3, R4, R5 and R6 are as described in claim 1 of the invention and a pharmaceutically acceptable salt thereof. The invention also relates to a medicinal agent for treating diseases associated with the binding site of the GABA A α5 receptor based on compounds of formula I and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds are active towards the binding site of said receptor and are useful in treating cognitive disorders such as Alzheimer's disease.

22 cl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I , wherein R2 means methyl, Y means carbon or nitrogen, and R1, R3 and R4 have the value specified in the patent claim. Also, the invention refers to a pharmaceutical composition for the use as a pharmaceutical drug having activity of a phosphatidylinositol-3-kinase inhibitor, to the use of the compounds of formula I for preparing the pharmaceutical drug for treating a disease mediated by phosphatidylinositol 3-kinase and to a method for preparing the compounds of formula I .

EFFECT: preparing the compounds of formula I possessing activity of the phosphatidylinositol-3-kinase inhibitor.

10 cl, 5 tbl, 51 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or use thereof to prepare a medicine for treating depression, anxiety or both: or pharmaceutically acceptable salts thereof, where m is 0-3; n is 0-2; Ar is: optionally substituted indolyl; optionally substituted indazolyl; azaindolyl; 2,3-dihydro-indolyl; 1,3-dihydro-indol-2-one-yl; optionally substituted benzothiophenyl; benzothiazolyl; benzisothiazolyl; optionally substituted quinolinyl; 1,2,3,4-tetrahydroquinolinyl; quinolin-2-one-yl; optionally substituted naphthalenyl; optionally substituted pyridinyl; optionally substituted thiophenyl or optionally substituted phenyl; R1 is: C1-6alkyl; hetero-C1-6alkyl; halo-C1-6alkyl; halo-C2-6alkenyl; C3-7cycloalkyl; C3-7cycloalkyl-C1-6alkyl; C1-6alkyl-C3-6cycloalkyl-C1-6alkyl; C1-6alkoxy; C1-6alkylsulphonyl; phenyl; tetrahydropyranyl-C1-6alkyl; phenyl-C1-3alkyl, where the phenyl part is optionally substituted; heteroaryl-C1-3alkyl; R2 is: hydrogen or C1-6alkyl; and each Ra and Rb is independently: hydrogen; C1-6alkyl; C1-6alkoxy; halo; hydroxy or oxo; or Ra and Rb together form C1-2alkylene; under the condition that, when m is 1, n is 2, and Ar is an optionally substituted phenyl, then R1 is not methyl or ethyl, and where optionally substituted denotes 1-3 substitutes selected from alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, amino, acylamino, monoalkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, pyrazolyl, -(CH2)q-S(O)rRf; -(CH2)q-C(=O)-NRgRh; -(CH2)q-N(Rf)-C(=O)-Ri or -(CH2)q-C(=O)-Ri; where q is 0, r is 0 or 2, each Rf, Rg and Rh is independently hydrogen or alkyl, and each Ri is independently alkyl, and where "heteroaryl" denotes a monocyclic radical having 5-6 ring atoms, including 1-2 ring heteroatoms selected from N or S, wherein the rest of the ring atoms are C atoms, "heteroalkyl" denotes an alkyl radical, including a branched C4-C7-alkyl, where one hydrogen atom is substituted by substitutes selected from a group consisting of -ORa, -NRbH, based on the assumption that the bonding of heteroalkyl radical occurs through a carbon atom, where Ra is hydrogen or C1-6alkyl, Rb is C1-6alkyl. Pharmaceutical compositions based on said compound are also disclosed.

EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.

14 cl, 1 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2-aza-bicyclo[3.3.0]octane derivative of formula , with stereogenic centres in a (1S,3S,5S)-configuration, where A is a thiazolyl which is unsubstituted or monosubstituted, where the substitute is independently selected from a group comprising C1-4alkyl, C3-6cycloalkyl and NH2; B is phenyl which is unsubstituted or mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, trifluoromethyl, NHC(O)CH3 and halogen; and R1 is an imidazo[2,1·b]thiazolyl or benzoisoxazolyl group, where said groups are independently unsubstituted or monosubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl; or R1 is a 2,3-dihydrobenzofuranyl group; or a pharmaceutically acceptable salt. The 2-aza-bicyclo[3.3.0]octane derivative of formula (I) is as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: obtaining novel 2-aza-bicyclo[3,3,0]octane derivatives as orexin receptor antagonists.

8 cl, 1 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where values of R, R1, R2, R3 and R4 are given in claim 1.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof in pharmaceutical compositions for treating sleep disorder.

10 cl, 1 tbl, 4 dwg, 153 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented nitrogen-containing heterocyclic compounds presented by the following formula wherein the radical values are specified in the description. These compounds or their pharmaceutically acceptable salts possess strong EP1 activity if introduced in a human or an animal; they are used as an effective component of a pharmaceutical agent, e.g. for preventing and/or treating overactive bladder.

EFFECT: compounds are used as an effective component of the pharmaceutical agent for preventing and/or treating the symptoms including frequent urination, heavy urination demand accompanied by fear of involuntary urination, and urinary incontinence.

24 cl, 145 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (I) in free form or in form of a pharmaceutically acceptable salt or solvate, which are useful in treating inflammatory or obstructive airways, pulmonary hypertension, pulmonary fibrosis, liver fibrosis, muscle diseases and systemic skeletal disorders and other diseases which are mediated by activity of the ALK-5 receptor or ALK-4 receptor. The invention also relates to a method of producing compounds of formula (I) and pharmaceutical compositions. In formula , T is a pyridin-2-yl which is optionally substituted in one position with R1; T1 is a pyridinyl which is optionally substituted in one or two positions with R1, R2, R5, C1-C4-alkoxy group, C1-C4-alkoxycarbonyl or cyano group; and Ra and Rb are independently hydrogen; C1-C8-alkyl, optionally substituted in one, two or three positions with R4; C3-C10-cycloalkyl, which is optionally substituted in one or two positions with a hydroxy group, amino group, C1-C8-alkyl, C1-C8-alkoxy group, halogen, cyano group, oxo group, carboxy group or nitro group; or C6-C15-aryl, optionally substituted in one, two or three positions with a halogen, hydroxy group, amino group, cyano group, oxo group, carboxy group, nitro group or R5; R1 is C1-C8-alkyl; R2 is C6-C15-aryl, optionally substituted in one, two or three positions with a halogen, hydroxy group, R1, R5, C1-C8-alkylthio group, amino group, C1-C8-alkylamino group, etc. The rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of using said compounds.

20 cl, 2 tbl

Cytokine inhibitors // 2485113

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to imidazole compounds of formula wherein the radical values A, X, R1, R2, R3 are presented in clause 1 of the patent claim.

EFFECT: there are disclosed pharmaceutical compositions of sail compounds for cytokine (eg TNFα or IL-1β) reduction.

16 cl, 107 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to isoxazole-pyridine derivatives of formula , where X; R1; R2, R3, R4, R5 and R6 are as described in claim 1 of the invention and a pharmaceutically acceptable salt thereof. The invention also relates to a medicinal agent for treating diseases associated with the binding site of the GABA A α5 receptor based on compounds of formula I and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds are active towards the binding site of said receptor and are useful in treating cognitive disorders such as Alzheimer's disease.

22 cl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted oxazolidinones of formula (I), wherein R1 means methyl, ethyl, n-propyl, methoxy, methoxymethyl or ethoxymethyl, R2 means hydrogen or methyl, and R3 means a group of formulas or , wherein * means an attachment point to an oxopyridine ring, n means number 1, 2, 3 or 4, m means number 1 or 2, R4 means hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyet-1-yl, 3-hydroxyprop-1-yl or 4-hydroxycyclohex-1-yl, R5 means hydrogen, methyl or ethyl, or R4 and R5 together with a nitrogen atom whereto attached, form a ring of morpholin-4-yl, a ring of 4-methyl-piperazin-1-yl or 4-hydroxy-piperidine-1-yl, R6 means hydrogen, cyclopropyl, cyclobutyl, 2-hydroxyet-1-yl, 3-hydroxyprop-1-yl, 2-methoxyet-1-yl, 3-methoyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl, R7 means hydrogen, methyl or ethyl, or R6 and R7 together with a nitrogen atom whereto attached, form a ring of pyrrolidin-1-yl, a ring of 2-methoxymethyl-pyrrolidin-1-yl, a ring of 1,1-dioxo-morpholin-4-yl, a ring of 1,4-oxazepan-4-yl, a ring of 4-methyl-piperazin-1-yl or 4-hydroxy-piperidine-1-yl, or to physiologically acceptable salts thereof. The invention also concerns a method for preparing said compounds.

EFFECT: there are prepared new compounds which can find application in medicine for treating and/or preventing the diseases caused by thrombembolia.

8 cl, 2 tbl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (1), wherein n means 0, 1, 2 or 3, R1 means chlorine, methyl, ethyl, n-propyl, methoxy, methoxymethyl or ethoxymethyl, R2 means hydrogen. The invention also refers to pharmaceutically acceptable salts of the compounds of formula (I) and to a method for preparing the compounds of formula (I).

EFFECT: preparing the compounds of formula (I) for treating and/or preventing thromboembolic diseases.

6 cl, 68 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1), in which Ar is a group of formula (Ar-1) or (Ar-2), in which R1 is a halogen, R2 is hydrogen, R3 is hydrogen, R4 is hydrogen, alkyl or alkenyl, X is a nitrogen atom or CH, R5 and R6 are each hydrogen and h equals 1; 1 equals 1 or 2; m equals 1 or 2; n equals 0, 1 or 2; o equals an integer from 0 to 3, under the condition that n and o are equal to 0 at the same time. Values of group A are as given in claim 1 of the invention. Described also is a pharmaceutical composition having agonistic activity with respect to 7 serotonin (5-HT4-receptors), which contains a compound of formula (1) and an agent which stimulates enterokinesis or improves functioning of the alimentary canal, which contains a compound of formula (1) as an active ingredient.

EFFECT: novel compounds are obtained and described, which have strong affinity towards 4 serotonin receptors, which are useful as an agent which stimulates enterokinesis or an agent which improves functioning of the alimentary canal.

28 cl, 233 ex, 29 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

, wherein X represents a halogen atom or C1-6-alkyl; and has the value of 0, 1, 2 or 3; R1 represents H; R2 represents or ; R3 represents C1-6-alkyl, C3-10-cycloalkyl, phenyl, 6-member heterocycloalkyl representing tetrahydropyranyl, or 5-10-member heteroaryl specified in pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzo[1,3]dioxolyl and 2,3-dihydrobenzo[1,4]dioxynyl; which be substituted and contains one to five substitutes specified in the patent claim. The invention also refers to pharmaceutical compositions possessing high affinity to dopamine D3 receptor and serotonin 5-HT2A receptor containing said compounds, and the use thereof in preparing drugs.

EFFECT: preparing the compounds of formula (I) possessing high affinity to dopamine D3 receptor and serotonine 5-HT2A receptor.

15 cl, 4 dwg, 5 tbl, 78 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a phenylpyrazol derivative presented by formula (1) or to its pharmaceutically acceptable salt: wherein R1 and R2, which may be identical or different, each represents C1-C6 alkyl, or R1 and R2 are coupled together with an adjacent nitrogen atom to form a 5-6-merous saturated heterocylic ring (wherein the mentioned saturated heterocylic ring may be substituted by halogen or C1-C6 alkyl), n represents an integer 0 to 2, T represents a hydrogen atom, halogen or C1-C6 alkyl, and R has one of formulas (I)-(V), (VII) or (VIII):

(wherein Z1 and Z2, which may be identical or different, each represents -CH2-, -O- or -NR11-, p represents an integer 0 to 3, q represents an integer 0 to 1, r and s which may be identical or different, which represents an integer 0 to 2, R3 represents halogen, C1-C6 alkyl, or hydroxy, R4 and R5 which may be identical or different, each represents a hydrogen atom, C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by hydroxy, hydroxy- C1-C6 alkoxy, C2-C7 alkoxycarbonyl or carboxy), or formula -(CH2)m-Ar1 (wherein Ar1 represents wherein (wherein said phenyl is substituted by halogen or C1-C6 alkyl), and m represents an integer 0 to 1), R6 represents oxo, R7 represents a hydrogen atom or C1-C6 alkyl, R8 represents C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by halogen), C1-C6 alkoxy (wherein said C1-C6 alkoxy is substituted by halogen) or formula -(CH2)1-Ar2 (wherein Ar2 represents phenyl (wherein said phenyl is substituted by C1-C6 alkoxy, hydroxyl or cyano) or pyridinyl, and 1 represents an integer O to 1), G represents -CO- or -SO2-, R9 represents C1-C6 alkyl, C1-C6 alkoxy, phenyl (wherein said phenyl may be substituted by halogen or pyridinyl, and R11 represents C1-C6 alkyl)}.

EFFECT: there are produced new compounds and a preventive or therapeutic agent on the basis of said compounds which can find application in medicine for treating dementia, Alzheimer's disease, attention deficit/hyperactivity disorder, schizophrenia, epilepsy, convulsions of central genesis, eating behaviour disorders, obesity, diabetes, hyperlipidemia, sleep disturbances, narcolepsy, sleeping apnoea syndrome, circadian rhythm disorder, depression or allergic rhinitis.

12 cl, 3 tbl, 72 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a compound having chemical formula or a salt thereof, where: Ar is an optionally substituted heteroaryl; R1 in each case is independently selected from a group which includes halogen, lower alkyl, optionally substituted with one or more substitutes selected from fluorine, lower alkoxy, fluorine-substituted lower alkoxy, monoalkylamino, dialkylamino, -O-R5, -N(R5)-R6 and -N(R5)-C(X)-R7; m equals 0 or 1; n equals 0, 1 or 2; R2 is hydrogen or a halogen; L2 is -S(O)2-; R3 is a lower alkyl, optionally substituted with fluorine, C3-6 cycloalkyl, optionally substituted with a lower alkyl, a 5- or 6-member nitrogen-containing heterocycloalkyl, optionally substituted with one or more substitutes selected from fluorine, lower alkyl, fluorine-substituted lower alkyl, lower alkoxy, fluorine-substituted lower alkoxy, lower alkylthio or fluorine-substituted lower alkylthio, aryl, optionally substituted with a halogen, lower alkyl, optionally substituted with a halogen or lower alkoxy, optionally substituted with a halogen, or a heteroaryl, optionally substituted with a halogen or a lower alkyl; L1 is selected from a group which includes -O-, -C(R12R13)-X-, -X-C(R12R13)-, -C(R12R13)-N(R11)-, -(R11)-C(R12R13)-, -C(X)-N(R11)-, -N(R11)-C(X)-; X is O; R11 is hydrogen; R4 is hydrogen or a lower alkyl; R5 and R6 in each case are independently selected from a group which includes hydrogen, lower alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, where each is optionally substituted with one or more substitutes selected from fluorine, lower alkoxy, fluorine-substituted lower alkoxy, lower alkylthio, fluorine-substituted lower alkylthio, monoalkylamino, dialkylamino; R7 in each case is independently selected from a group which includes lower alkyl; where the terms "lower alkyl", "lower alkoxy", "lower alkylthio", "monoalkylamino", "dialkylamino", "cycloalkyl", "heterocycloalkyl", "aryl", "heteroaryl", are as described in the claim. The invention also discloses a pharmaceutical composition for treating Raf kinase mediated diseases which is based on a compound of formula I; use of the compound of formula I to produce a medicinal agent is also disclosed.

EFFECT: novel compound which can be useful in treating diseases and conditions associated with aberrant activity of protein kinases is obtained and described.

9 cl, 13 ex, 2 tbl

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