Novel 2-aminooxazolines as taar1 ligands

FIELD: chemistry.

SUBSTANCE: invention is a 6-10-member aryl selected from phenyl, naphthyl, tetrahydronaphthalenyl, indanyl or a 6-member heteroaryl containing 1-2 N atoms, selected from pyridyl or pyrimidinyl, where the aryl and heteroaryl groups can be unsubstituted or substituted with 1-3 substitutes selected from a group consisting of C3-6-cycloalkyl, phenyl, phenyloxy, benzyl, benzyloxy, halogen atom, C1-7-alkyl, C1-7-alkoxy, oxazolyl, piperidin-1-yl, or C1-7-alkyl, substituted with a halogen atom, or represents phenyl, where at least one hydrogen atom is substituted with deuterium or tritium; R2 is a hydrogen atom, C1-7-alkyl or is benzyl, unsubstituted or substituted C1-7-alkoxy or halogen atom; or R1 and R2 together with a N atom with which they are bonded form 2,3-dihydroindol-1-yl or 3,4-dihydro-1quinolin-1-yl. The invention also relates to a method of producing compounds of formula and to a pharmaceutical composition having high affinity for the TAAR1 receptor.

EFFECT: compounds of formula (I), having high affinity for the TAAR1 receptor.

29 cl, 4 dwg, 1 tbl, 183 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula
,
where R1is a 6-10-membered aryl, selected from phenyl, naphthyl, tetrahydronaphthalene, indanyl, or 6-membered heteroaryl containing 1-2 N atom selected from pyridyl or pyrimidinyl, where aryl and heteroaryl groups can be unsubstituted or can be substituted one to three substituents selected from the group consisting of C3-6-cycloalkyl, phenyl, phenyloxy, benzyl, benzyloxy, halogen atom, 1-7-alkyl, C1-7-alkoxy, oxazole, piperidine-1-yl, or1-7-alkyl, substituted by a halogen atom, or represents phenyl, where at least one hydrogen atom is replaced by deuterium or tritium;
R2represents a hydrogen atom, a C1-7-alkyl or represents benzyl, unsubstituted or substituted C1-7-alkoxy or halogen atom; or
R1and R2together with the N atom to which they are attached form a 2,3-dihydroindol-1 yl or 3,4-dihydro-quinoline-1-yl;
or its pharmaceutically acceptable salt accession acid.

2. The compound of formula I according to claim 1, where R1represents unsubstituted phenyl and R2represents a C1-7-alkyl.

3. The compound of formula I according to claim 2, which is a
(R)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine or
(S)-4-[(methyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine.

4. The compound of formula I according to claim 1, where R1represents phenyl substituted by a halogen atom, and R2represents a C1-7-alkyl.

5. The compound of formula I according to claim 4, which is a
(S)-4-{[(3,4-dichloro-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-chloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(3,4-dichloro-phenyl)-isopr the peel-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-bromo-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-bromo-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(3,4-dichloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(3-bromo-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(3-bromo-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(3-chloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-chloro-2-fluoro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-chloro-2-fluoro-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[ethyl-(2-fluoro-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(2-chloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(4-chloro-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(4-chloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(4-fluoro-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(4-chloro-phenyl)-isopropyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(2,4-debtor-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(2,4-debtor-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(3,4-dichloro-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(3,4-dichloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(3,4-dichloro-phenyl)-isopropyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(3,5-dichloro-what enyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine or
(S)-4-{[(3,5-dichloro-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine.

6. The compound of formula I according to claim 1, where R1represents phenyl substituted by a halogen atom or CF3and R2represents a hydrogen atom.

7. The compound of formula I according to claim 6, which is a
(S)-4-[(3-chloro-phenylamino)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(2-chloro-phenylamino)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(4-trifluoromethyl-phenylamino)-methyl]-4,5-dihydro-oxazol-2-ylamine or
(S)-4-[(2,4-debtor-phenylamino)-methyl]-4,5-dihydro-oxazol-2-ylamine.

8. The compound of formula I according to claim 1, where R1represents phenyl substituted by a halogen atom and C1-7-alkyl, and R2represents a hydrogen atom.

9. The compound of formula I of claim 8, which is a
(S)-4-[(2-fluoro-4-methyl-phenylamino)-methyl]-4,5-dihydro-oxazol-2-ylamine.

10. The compound of formula I according to claim 1, where R1represents phenyl, substituted CF3and C1-7the alkyl or only CF3and R2represents a C1-7-alkyl.

11. The compound of formula I of claim 10, which is a
(S)-4-{[ethyl-(4-trifluoromethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[methyl-(4-trifluoromethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine or
(S)-4-{[ethyl-(2-methyl-4-trifluoromethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine.

12. Obedinenie formula I according to claim 1, where R1represents pyridin-2-yl, and R2represents a C1-7-alkyl.

13. The compound of formula I according to item 12, which is a
((S)-2-amino-4,5-dihydro-oxazol-4-ylmethyl)-(6-chloro-pyridine-2-yl)-amine.

14. The compound of formula I according to claim 1, where R1represents phenyl, substituted simultaneously by a halogen atom and methoxy.

15. The compound of formula I through 14, which is a
(S)-4-{[(4-chloro-3-methoxy-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-chloro-3-methoxy-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[(4-fluoro-3-methoxy-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(4-fluoro-3-methoxy-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[ethyl-(4-fluoro-3-methoxy-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(R)-4-{[(4-chloro-3-methoxy-phenyl)-methyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine or
(R)-4-{[(4-chloro-3-methoxy-phenyl)-ethyl-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine.

16. The compound of formula I according to claim 1, where R1represents phenyl, substituted simultaneously by a halogen atom and a methoxy or a halogen atom, and R2represents benzyl.

17. The compound of formula I according to item 16, which is a
(S)-4-{[benzyl-(4-fluoro-3-methoxy-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[benzyl-(4-fluoro-phenyl)-amino]-methyl}-4,5-dihydro-ACS is evil-2-ylamine or
(S)-4-{[benzyl-(4-chloro-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine.

18. The compound of formula I according to claim 1, where R1represents phenyl, substituted C1-7-alkyl, and R2represents a C1-7-alkyl.

19. The compound of formula I according p, where the connection specified is a
(S)-4-[(ethyl-meta-tolyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(S)-4-{[ethyl-(3-ethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine or
(S)-4-{[ethyl-(4-ethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine.

20. The compound of formula I according to claim 1, where R1represents naphthyl, and R2represents a C1-7-alkyl.

21. The compound of formula I according to claim 20, where the connection specified is a
(S)-4-[(methyl-naphthalene-2-yl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine,
(R)-4-[(methyl-naphthalene-2-yl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine or
(R)-4-[(ethyl-naphthalene-2-yl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine.

22. The compound of formula I according to claim 1, where R1represents phenyl substituted by a halogen atom and CF3.

23. The compound of formula I according to article 22, where the connection specified is a
(S)-4-{[ethyl-(3-fluoro-5-trifluoromethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine,
(S)-4-[(3-fluoro-4-trifluoromethyl-phenylamino)-methyl]-4,5-dihydro-oxazol-2-ylamine or
(R)-4-{[ethyl-(3-fluoro-5-trifluoromethyl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-ylamine.

24. The compound of formula I according to claim 1, where R1represents indanyl, and R2represents a C1-7-alkyl.

25. The compound of formula I according to paragraph 24, where the connection specified is a
(S)-4-[(ethyl-indan-5-yl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine.

26. The compound of formula I according to claim 1, where R1represents phenyl, substituted heteroaryl.

27. The compound of formula I according p, where the connection specified is a
(S)-4-{[methyl-(3-oxazol-5-yl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine or
(S)-4-{[ethyl-(3-oxazol-5-yl-phenyl)-amino]-methyl}-4,5-dihydro-oxazol-2-ylamine.

28. Method of producing compounds of the formula I, which includes
a) interaction of the compounds of formula

and bromine cyan obtaining the compounds of formula
,
where definitions are as described in claim 1, or
b) removing the protective group from compounds of the formula
,
where R2represents benzyl or benzyl, substituted alkoxy,
obtaining the compounds of formula
,
where definitions are as described in claim 1, or
if desired, the conversion of the compounds obtained into pharmaceutically acceptable salts accession acids.

29. Pharmaceutical composition having high affinity of the receptor TAAR1, containing one or more than one compound of formula I in an effective amount and a pharmaceutically acceptable excipients.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are produced new diazepane substituted compounds representing various heterocyclic systems, including condensed, pharmaceutical compositions containing said compounds.

EFFECT: producing the compounds and compositions for preventing and treating neurological and mental disorders and diseases with involved orexin receptors.

13 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel cyanoisoquinoline derivatives of formula I , where R is selected from a group comprising hydrogen and C1-C10 alkyl, R1, R2, R3 and R4 are independently selected from a group comprising hydrogen, halogen, hydroxy, C1-C10 alkyl, substituted with 1-3 halogen atoms or C6-C14 acryl, C6-C14 aryl, -OR7, -SR7 and -SO2R7, where R7 is selected from a group comprising C1-C10 alkyl, C1-C10 alkyl substituted with C6-C14 aryl, C3-C10 cycloalkyl, C6-C14 aryl and C7-C8 heteroaryl containing 1-2 heteroatoms selected from a group comprising N, O and S, where C6-C14 aryl and C7-C8 heteroaryl are optionally substituted with 1-3 substitutes selected from a group comprising halogen, C1-C6 alkoxy, C1-C10 alkyl, C1-C6 dialkylamino and C4 heterocyclyl containing 2 heteroatoms selected from a group comprising nitrogen and oxygen, and R5 and R6 are independently selected from a group comprising hydrogen and C1-C3 alkyl, or pharmaceutically acceptable salts thereof. The invention also relates to novel cyanoquinoline derivatives of formula II , where R31, R32, R33 and R34 are independently selected from a group comprising hydrogen, hydroxy, halogen, C1-C10 alkyl substituted with 1-3 halogen atoms or with C6-C14 aryl, C6-C14 aryl, -OR37, -SR37 and -SO2R37, where R37 is selected from a group comprising C1-C10 alkyl, C1-C10 alkyl substituted with C6-C14aryl, C3-C10 aryl, C7-C8 heteroaryl containing 1-2 heteroatoms selected from a group comprising N, O and S, where C6-C14 aryl and C7-C8 heteroaryl are substituted with 1-3 substitutes selected from a group comprising halogen, C1-C6 alkoxy, C1-C10 alkyl, C1-C6 dialkylamino C4 heterocyclyl containing 2 heteroatoms selected from a group comprising nitrogen and oxygen, R35 denotes hydrogen or methyl, or pharmaceutically acceptable salts thereof. The invention also relates to specific cyanoisoquinoline compounds, a pharmaceutical composition based on the compound of formula I, a hypoxia-inducible factor (HIF) hydroxylase inhibiting method, a method of treating, preventing or slowing down development of a condition associated with hypoxia-inducible factor (HIF), a condition associated with erythropoietin (EPO), anaemia, based on use of the compound of formula I.

EFFECT: obtaining novel cyanoisoquinoline compounds having useful biological properties.

42 cl, 1 tbl, 54 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I): wherein n means 1 or 2, X means an oxygen atom, a sulphur atom or NH, R1 means a side group of natural α-amino acid or its homologues or isomers specified in hydrogen, methyl, propan-2-yl, propan-1-yl, 2-methyl-propan-1-yl, imidazol-4-ylmethyl, hydroxymethyl, 1-hydroxy-ethyl, carboxymethyl, 2-carboxyethyl, carbamoyl-methyl, 2-carbamoyl ethyl a, 4-aminobutan-1-yl, 3-aminopropan-1-yl, 3-guanidinopropan-1-yl, benzyl or 4-hydroxybenzyl, R2 means hydrogen or methyl, R3 means hydrogen, or R1 and R3 are coupled together by the group (CH2)3- or (CH2)4- and together with nitrogen and carbon atoms whereto attached form a five- or six-member ring, as well to their salts, solvates and salt solvates.

EFFECT: preparing compounds for treating and/or preventing the diseases, first of all thromboembolic diseases.

2 cl, 2 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing optionally substituted 4-(benzimidazo-2-yl methylamino)benzamidine of formula (I) in which R1 denotes a methyl group, R2 denotes a R21NR22 group, where R21 denotes an ethyl group which is substituted with an ethoxycarbonyl group, and R22 denotes a pyridin-2-yl group, R3 denotes an n-hexyloxycarbonyl group, where at step (a) phenyldiamine of formula (II) where R1 and R2 assume values given for formula (I), which reacts with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid, to obtain a product of formula (III) where R1 and R2 assume values given for formula (I), which is hydrogenated at temperature from 30 to 60°C at hydrogen pressure from 1 to 10 bar, over palladium on activated charcoal (Pd/C) in a mixture of tetrahydrofuran and water, and then, without any preliminary extraction of the hydrogenation product, the obtained compound of formula (I), in which R3 denotes hydrogen, in the presence of potassium carbonate reacts with a compound of formula (IV) R3-X (IV), where R3 assumes values given for formula (I), and X denotes a suitable splitting group.

EFFECT: simple method of producing optionally substituted 4-(benzimidazo-2-yl methylamino)benzamidine.

3 cl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new piperazine amide derivatives of formula wherein X represents N or CH; Y represents N or CH; R1 represents lower alkyl, phenyl, phenyl-lower alkyl wherein phenyl can be optionally substituted by 1-2 substitutes independently specified in a group consisting of halogen, lower alkyl; R2 represents lower alkyl, phenyl, naphthyl or heteroaryl specified in dimethylisoxazolyl, quinolinyl, thiophenyl or pyridinyl wherein phenyl or heteroaryl are optionally substituted by 1 substitute optionally specified in a group consisting of halogen, lower alkoxy group, fluor-lower alkyl, lower alkoxy-carbonyl and phenyl; R3 represents phenyl, pyridinyl or pyrazinyl wherein phenyl, pyridinyl or pyrazinyl are substituted by 1-2 substituted optionally specified in a group consisting of halogen, lower alkyl and fluor-lower alkyl; R4, R5, R6, R7, R8, R9, R10 and R11 independently represent hydrogen, as well as to their physiologically acceptable salts. These compounds are bound with LXR alpha and LXR beta, and are applicable as therapeutic agents for treatment and/or prevention of high lipid levels, high cholesterol levels, low HDL cholesterol, high LDL cholesterol, atherosclerotic diseases, diabetes, non insulin dependent diabetes mellitus, metabolic syndrome, dislipidemia, sepsis, inflammatory diseases, infectious diseases, skin diseases, colitis, pancreatitis, cholestasis, liver fibrosis, psoriasis, Alzheimer's disease, etc.

EFFECT: preparing new piperazine amide derivatives.

15 cl, 88 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula , where R1 denotes OH, OPO3H2 or OCOR5; R2 denotes H, OH or OPO3H2; A denotes N or CR6; R3 denotes fluorine; R4 denotes H, C1-3alkyl or C3-6cycloalkyl; R5 denotes an alanine residue; R6 denotes H, C1-6alkoxy group or halogen; and n=0 or 1; and to pharmaceutically acceptable salts of compounds of formula I. The invention also relates to a pharmaceutical composition having antibacterial activity, and to use of compounds of formula I to obtain a medicinal agent for preventing or treating bacterial infections.

EFFECT: compounds of formula I, having antibacterial activity.

14 cl, 3 dwg, 2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I):

, where: R=NO2, or and Het denotes an azolyl radical selected from nitroazolyl and tetrazolyl radicals; except 3- and nitro-4-(4-nitro-1,2,3-triazol-1-yl)furazan. The invention also describes a method of producing a compound of formula I and an energy composition based on said compounds.

EFFECT: compounds have high energy characteristics, low sensitivity and high thermal stability.

11 cl, 7 ex, 3 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention describes isoxazolines of formula (I), in which A denotes C or N; R denotes C1-4 haloalkyl; X denotes identical or different halogens or C1-4 haloalkyl; l equals 0, 1 or 2; Y denotes halogen or C1-4 alkyl, C1-4alkoxy, C1-4haloalkyl, cyano, nitro, amino, C1-4 alkylcarbonylamino, benzoylamino or C1-4 alkoxycarbonylamino; m equals 1 or 1; and G denotes any group selected from heterocyclic groups given in the description, and a method of producing said compounds and use as insecticides for controlling the population of harmful insects or arthropods.

EFFECT: high efficiency of using said compounds.

11 cl, 28 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel azoles of general formula 1A and 1B and pharmaceutically acceptable salts thereof, having activity on hepatitis C and hepatitis GBV-C virus. Said compounds have NS5A viral protein ligand properties and can be used as active components for a pharmaceutical composition and a medicinal agent for treating diseases caused by said viruses. In general formula 1A and 1B, the solid lines accompanied by dotted lines denote a single or double bond, wherein if one of them is a single bond, the other is a double bond; X and Y optionally assume different values and denote a nitrogen, oxygen or sulphur atom or a NH group; R1 and R2 optionally denote identical radicals 2.1-2.20, in which the asterisk (*) indicates site of the bond to azole fragments. Said fragments and values of A and B are given in the claim.

EFFECT: more value of the compounds.

10 cl, 1 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: this invention relates to new compounds with formula (I) possessing the properties of mGLuR2 antagonists, to their obtainment methods, their application for production of medicines for prevention and treatment of disorders wherein mGLuR2 plays the activation role (in particular - central nervous system disorders). In formula (I) either any of X and Y represents N while the other represents CH or each of X and Y represents N; A represents aryl representing phenyl or 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur, the heteroaryl selected from among amidazolyl, [1,2,4] oxadiazolyl, pyrrolyl, 1H-pyrazolyl, pyridinyl, [1,2,4] triazolyl, tiazolyl and pyrimidinyl, each of them substitutable by C1-6-alkyl; B represents H, cyano or represents a possibly substituted aryl selected from among phenyl or possibly substituted by 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur where the substitutes are selected from the group consisting of nitro, C1-6-alkyl, possibly substituted hydroxy, NRaRb where Ra and Rb independently represent H, C1-6-alkyl etc. R1 represents H, a halogen atom, C1-6-alkyl, possibly substituted hydroxy, C1-6-alcoxy, C1-6-halogenoalkyl, C3-6-cycloalkyl represents H cyano, a halogen atom, C1-6-halogenoalkyl, C1-6-alcoxy, C1-6-halogenoalcoxi-, C1-6-alkyl or C3-6-cycloalkyl R3 represents a halogen atom, H, C1-6-alcoxy, C1-6-halogenoalkyl, C1-6-alkyl, C3-6-cycloalkyl, C1-6-halogenoalcoxy R4 reprsents H or halogeno.

EFFECT: creation of new compounds of formula (I) possessing mGLuR2 antagonist properties.

104 cl, 465 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new substituted heteroaryl derivatives of general formula I: , wherein: A means N, CR7-10, with A at the most twice meaning N; W means O, S or NR4, the values B, C, R7-10 are presented in clause 1 of the patent claim. The method for preparing the compound I is described.

EFFECT: compounds show analgesic activity that enables using them for a variety of diseases, especially acute pain, neuropathic, chronic or inflammatory pain.

16 cl, 2 tbl, 307 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazole derivatives of formula I wherein R1 represents a hydrogen atom or C1-7alkyl; R2 represents C1-7alkyl; R3 represents C1-7alkyl, C1-7alkoxy, phenyloxy, benzyloxy, a halogen atom or C1-7alkyl substituted by a halogen atom; R4 represents a hydrogen atom or C1-7alkyl; X represents -CH2-, -CHR2 - or -O; Y represents -CH2-, -CH2CH2- or a bond; provided X represents -O-, Y represents -CH2-; Z represents -CH2- or -CHR2-; provided R2 is found twice, simultaneously for X and Z which are CHR2 , then R2 can be identical alkyls or different; n has the value 0, 1 or 2; provided n has the value 2, R3 can be identical or different; and its pharmaceutically acceptable acid addition salts, except for the following compounds: 1-(1H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydro-quinoline and 1-(3H-imidazol-4-ylmethyl)-2,3-dihydro-1H-indole. Also, the invention refers to a method for preparing the compounds of formula I, to a drug based on the compound of formula I and applying the compound of formula I in preparing the drug.

EFFECT: there are prepared new imidazole derivatives effective in treating such pathological conditions, as bipolar disorder, stress-induced disorder, psychotic disorders, schizophrenia, neurological conditions, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease.

13 cl, 61 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (II)

or to its pharmaceutically acceptable salt wherein the ring A represents a group presented by formula 2 R1 represents hydrogen or C1-6alkyl; R2 represents -SR5, halogen, halogenated C1-6alkyl, etc., R3 represents a group presented by formula: -CH=CH-C(RaRb)-Rc-Rd, or a group presented by formula: -(CReRf)m-C(RaRb)-Rc-Rd wherein radicals and symbols have the values presented in the patent claim, R4 represents -OR6, -CONR7R8, -NR9CONR7R8, -(CR10R11)POH, -(CR10R11)pOCONR7R8, -NR9COR12, -(CR10R11)pNR9COR12, -C(=O)NR9OR12, -CONR9CONR7R8, -CN, halogen or NR9(C=O)OR12; R5 represents C1-6alkyl; R6 represents -CONR7R8; each of R7 and R8 independently represents hydrogen or etc., R10 and R11 independently represents hydrogen; R12 represents C1-6alkyl; each of m and p independently represents an integer 1 to 3. This compound is applicable as a type 1 11β-hydroxysteroiddehydrogenase inhibitor.

EFFECT: invention also refers to single compounds, pharmaceutical compositions on the basis of the declared compounds, to a method for preventing and treating diabetes and the use of the compound of formula (II).

21 cl, 289 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel clathrate complex of β-cyclodextrin with 1-{[6-bromo-1-methyl-5-methoxy-2-phehylthiomethyl-1-H-indol-3-yl]carbonyl}-4-benzylpiperazine of formula : with molar ratio 1-{[6-bromo-1-methyl-5-methoxy-2-phehylthiomethyl-1-H-indol-3-yl]carbonyl}-4-benzylpiperazine: β-cyclodextrin from 1:1 to 1:10, synthesis method and use thereof as an antiviral agent for treating influenza. The disclosed method involves mixing solutions of β-cyclodextrin and 1-{[6-bromo-1-methyl-5-methoxy-2-phehylthiomethyl-1-H-indol-3-yl]carbonyl}-4-benzylpiperazine in molar ratio from 1:1 to 1:10 while stirring and heating to temperature not higher than 70°C and then maintaining said conditions until a homogeneous solution is obtained and extraction of the obtained complex.

EFFECT: clathrate complex is a novel effective anti-influenza virus agent which is obtained using a novel efficient method.

13 cl, 2 ex, 3 tbl, 11 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for synthesis of 2-substituted azole

compounds of formula , (a) reaction of an aldehyde of formula

with an azole of formula in the presence of a carbonylating agent of formula to obtain an oxazolidone of formula , reaction of the oxazolidone of formula (Ia) so as to perform hydrolysis of a triarylmethyl group, splitting the O-(C=Q) bond and opening the oxazolidone, followed by reaction of the obtained intermediate compound with Prot-Z, where Prot-Z is an agent which protects an amino group, to obtain an azole-containing intermediate compound of formula (lb) and and oxidation of the intermediate compound of formula (Ib) to obtain a 2-substituted azole derivative of formula (I). The invention also relates to azole compounds of formulae (I), (la), (lb), (Ic) and (II).

EFFECT: novel method of obtaining azoles of formula (I), as well as obtaining novel compounds of formulae (I), (la), (lb), (Ic) and (II), having useful biological properties.

41 cl, 5 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I:

or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.

EFFECT: improved properties of compounds.

27 cl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

and pharmaceutically acceptable salts and solvates thereof, in which R1 is an optionally substituted alkyl or similar, R2 is a group of formula: -Y-R5, where Y is -O- or S; R5 is a substituted alkyl (the substitute is an optionally substituted cycloalkyl or similar), a branched alkyl or similar; R4 is hydrogen or C1-10 alkyl; R3 is a group of formula: -C(=O)-Z-R6, where Z is -NR7- or -NR7-W-; R6 is an optionally substituted cycloalkyl or similar; R7 is hydrogen or C1-10 alkyl, W is C1-10 alkylene; X is =N- provided that a compound in which R2 is 2-(4-morpholino)ethoxy, 2-, 3- or 4-pyridylmethoxy, 1-methylpiperidinyl-2-methoxy, benzyloxy or 4-substituted benzyloxy is excluded; and R3 is N-(1-adamantyl)carbamoyl, N-(2-adamantyl)carbamoyl and N-(3-noradamantyl)carbamoyl. Said compound is an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. The invention also relates to a pharmaceutical composition containing said compound as an active ingredient.

EFFECT: improved properties of the compound.

23 cl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I): where R1 and R2 represent hydrogen and a group which is hydrolysed in a physiological environment, optionally substituted lower alkanoyl or aroyl; X represents a methylene group; Y represents oxygen atom; n represents the number 0, 1, 2 or 3 and m represents the number 0 or 1; R3 represents a group of pyridine N-oxide according to formula A, B or C which is attached as shown by an unmarked linking: where R4, R5, R6 and R7 independently represent aryl, heterocycle, hydrogen, C1-C6-alkyl, C1-C6-alkylthio, C6-C12-aryloxy or C6-C12-arylthio group, C1-C6-alkylsulphonyl or C6-C12-arylsulphonyl, halogen, C1-C6-haloalkyl, trifluoromethyl, or heteroaryl group; or where two or more residues R4, R5, R6 and R7 taken together represent an aromatic ring, and where P represents a central part, preferentially chosen from regioisomers 1,3,4-oxadiazol-2,5-diyl, 1,2,4-oxadiazol-3,5-diyl, 4-methyl-4H-1,2,4-triazol-3,5-diyl, 1,3,5-triazine-2,4-diyl, 1,2,4-triazine-3,5-diyl, 2H-tetrazol-2,5-diyl, 1,2,3-thiadiazol-4,5-diyl, 1-alkyl-3-(alkoxycarbonyl)-1R-pyrrol-2,5-diyl, where alkyl is presented by methyl, thiazol-2,4-diyl, 1H-pyrazol-1,5-diyl, pyrimidine-2,4-diyl, oxazol-2,4-diyl, carbonyl, 1H-imidazol-1,5-diyl, isoxazol-3,5-diyl, furan-2,4-diyl, benzole-1,3-diyl and (Z)-1-cyanoethene-1,2-diyl, and where the regioisomers of the central part include both regioisomers produced by exchanging the nitrocatechol fragment and the -(X)n-(Y)m-R3 fragment. Also, the invention refers to a method for making a compound of formula I, as well as to a method for treating an individual suffering central and peripheral nervous system disorders, to a pharmaceutical composition based on the compounds of formula I, and also to their application for preparing the drug and as COMT inhibitor.

EFFECT: there are produced and described new compounds which show a potentially effective pharmaceutical properties in treating a number of central and peripheral nervous system disorders.

25 cl, 64 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), in which (i) R1 denotes C1-C6-alkyl or hydrogen; and R2 denotes hydrogen or a -R7, -Z-Y-R7, -Z-NR9R10, -Z-CO-NR9R10, -Z-NR9-C(O)O-R7 or -Z-C(O)-R7 group; and R3 denotes an undefined pair or C1-C6-alkyl; or (ii) R1 and R3 together with a nitrogen atom with which they are bonded form a 5-6-member heterocycloalkyl ring; and R2 denotes an undefined pair or a -R7 , -Z-Y-R7 group; or (iii) R1 and R2 together with a nitrogen atom with which they are bonded form a 6-member heterocycloalkyl ring, where said ring is substituted with a -Y-R7 group, and R3 denotes an undefined pair or C1-C6-alkyl; R4 and R5 are independently selected from a group consisting of phenyl, C3-C6-cycloalkyl; R6 denotes -OH, C1-C6-alkyl, C1-C6-alkoxy or a hydrogen atom; A denotes an oxygen or sulphur atom; X denotes a C1-C6-alkylene group; R7 denotes C1-C6-alkyl, phenyl, phenyl(C1-C6-alkyl)-, dihydrobenzofuran or pyridine, where any phenyl in group R7 can be optionally substituted with one or two groups independently selected from halogen, aminoacyl, C1-C6-alkoxycarbonyl, aminosulphonyl, C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, -COOH; and any pyridine in group R7 can be optionaly substituted with C1-C6-alkyl; R8 denotes C1-C6-alkyl or a hydrogen atom; Z denotes a C1-C10-alkylene or C2-C10-alkenylene group; Y denotes a bond or an oxygen atom; R9 and R10 independently denote a hydrogen atom, C1-C6-alkyl group, isoxazole or 8-hydroxy-1H-quinolin-2-one-(C1-C6-hydroxyalkyl); and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition having activity with respect to M3 muscarinic receptor; use of the compounds of formula (I) to produce a medicinal agent for treating and a method of treating diseases or conditions in which M3 muscarinic receptor activity is involved.

EFFECT: compounds of given formula have activity with respect to M3 muscarinic receptor.

26 cl, 8 dwg, 91 ex

FIELD: chemistry.

SUBSTANCE: invention relates to tetrahydroquinoline derivatives of formula (I), where values of C3-C4, R2, R3, R4, R5, L1, L2, Y and X are given in claim 1, as muscarinic receptor agonists; compositions containing said compounds; methods of inhibiting muscarinic receptor activity using said compounds; methods of treating diseased conditions associated with the muscarinic receptor using said compounds, and methods of identifying a subject suitable for treatment using said compounds.

EFFECT: improved properties of compounds.

22 cl, 1 tbl, 3 ex, 3 dwg

The invention relates to imidazole derivative of formula (1), where X, Y, R, R2, R3and R4such as defined in the claims
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