Benzylpyridazinones as inhibitors of reverse transcriptase

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention concerns bonds, applicable for treatment of diseases mediated by the HIV virus, formula I where X1 is chosen from R5O, R5S(O)n, R5CH2, R5CH2O, R5CH2S(O)n, R5OCH2 and R5S(O)nCH2; R1 and R2 are chosen from H, NH2, alkyl, haloalkyl, cycloalkyl, alkoxy, alkylthio, halogen, alkylamino, dialkylamino, nitro and cyano; or in common form-CH=CH-CH=CH- or five-term heterocycle with the heteroatom chosen from O and S; R3 is chosen from H, halogen, nitro and cyano; R4 is chosen from H, NH2, alkyl, haloalkyl, cycloalkyl, alkoxy, alkylthio, halogen, alkylamino, dialkylamino, nitro and cyano; R5 the pyridine-N-oxide, indole, chinoline, chinoline-N-oxide is chosen from alkyl, cycloalkyl and unessentially replaced phenyl, naphthyl, pyridinil; R7 and R8 are chosen from H, NH2, an alkylamin, dialkylamine and unessentially substituted C1-C6alkyl; n is chosen from 0, 1, 2.

EFFECT: obtaining of new inhibitors by reverse transcriptase.

2 cl, 46 ex, 3 tbl

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

in which

X1selected from the group comprising R5O, R5S(O)n, R5CH2, R5CH2O, R5CH2S(O)n, R5OCH2and R5S(O)nCH2;

R1and R2mean

(i) the substituents, independently selected from the group comprising hydrogen, C1-C6alkyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup, C1-C6allylthiourea, halogen, amino, C1-C6alkylamino, C1-C6dialkylamino, the nitro-group and cyano; or

(ii) taken together represent-CH=CH-CH=CH-, or

(iii) taken together with the carbon atoms to which they are attached, form a 5-membered heteroaromatic or heterocyclic ring containing 1 heteroatom independently selected from O and S;

R3selected from the group comprising hydrogen, halogen, the nitro-group and cyano;

R4selected from g is PI, including hydrogen, C1-C6alkyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup,1-C6allylthiourea, halogen, amino, C1-C6alkylamino, C1-C6dialkylamino, aminoacyl, nitro-group and cyano;

R5selected from the group comprising C1-C6alkyl, C3-C8cycloalkyl, phenyl, naphthyl, pyridinyl, pyridine-N-oxide, indole, quinoline, quinoline-N-oxide; where mentioned phenyl, naftalina, pyridinoline, pyridine-N-oxide, indole, quinoline, quinoline-N-oxide group optionally contain from 1 to 3 substituents independently selected from the group comprising C1-C6alkyl, C1-C6alkenyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup, C1-C6allylthiourea, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, hydroxy-group, halogen, an amino group, a C1-C6alkylamino, C1-C6dialkylamino, carbarnoyl, the nitro-group and cyano;

R7and R8independently selected from the group comprising hydrogen, an amino group, a C1-C6alkylamino,1-C6dialkylamino and C1-C6alkyl, optionally containing 1 or Deputy, independently selected from the group comprising a hydroxy-group and halogen;

n denotes an integer from 0 to 2; and

it hydrates, solvate, and salts with acids, provided that the compound is not 3-(3-methoxybenzyl)-1,6-dihydro-6-pyridazinone.

2. The compound according to claim 1, in which R5selected from the group comprising From1-C6alkyl, C3-C8cycloalkyl, phenyl, naphthyl, pyridinyl; and these phenyl, naftalina and pyridinoline group optionally contain from 1 to 3 substituents independently selected from the group comprising C1-C6alkyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup, C1-C6allylthiourea, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, halogen, C1-C6alkylamino, C1-C6dialkylamino and cyano.

3. The compound according to claim 2, in which X1indicates OR5or SR5; R3denotes hydrogen or fluorine; R4selected from the group comprising hydrogen, chlorine, fluorine and methyl; R5denotes optionally substituted phenyl; and R7and R8selected from the group comprising hydrogen, an amino group, a C1-C6alkylamino,1-C6dialkylamino and C1-C6alkyl, optionally substituted hydroxycu who sing, halogen.

4. The compound according to claim 3 in which R1denotes methyl, ethyl, trifluoromethyl or halogen.

5. The compound according to claim 4, in which R5represents monosubstituted phenyl.

6. The compound according to claim 4, in which R5denotes a 2,5-disubstituted phenyl.

7. The compound according to claim 4, in which R5denotes a 3,5-disubstituted phenyl.

8. The compound according to claim 4, in which R5denotes a 2,4-disubstituted phenyl.

9. The compound according to claim 4, in which R5denotes a 2,6-disubstituted phenyl.

10. The compound according to claim 2, in which X1means-OR5or-SR5; R1and R2independently selected from the group comprising hydrogen, C1-C6alkyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup,1-C6allylthiourea, halogen, amino, C1-C6alkylamino,1-C6dialkylamino, the nitro-group and cyano; and R3denotes hydrogen or fluorine.

11. The connection of claim 10, in which X1indicates OR5; R1denotes methyl, ethyl, trifluoromethyl or halogen; R2and R4denote hydrogen, fluorine, chlorine, methyl or ethyl; R3denotes hydrogen or fluorine; R7denotes hydrogen, methyl or ethyl; and R8selected from the group comprising hydrogen, the amino group, With1-C6alkylamino is, C1-C6dialkylamino and C1-C6alkyl, optionally substituted by a hydroxy-group, halogen.

12. Connection by claim 11, in which R5represents monosubstituted phenyl.

13. The connection section 12, in which R5represents monosubstituted phenyl and Deputy selected from the group comprising halogen, cyano, C1-C6alkyl, C1-C6alkenyl,3-C8cycloalkyl, C1-C6halogenated, C1-C6alkoxygroup,1-C6allylthiourea.

14. The connection 13, in which R1selected from the group comprising halogen, methyl, ethyl, R3and R7denote hydrogen, R5represents monosubstituted phenyl and Deputy selected from the group comprising halogen, cyano, C1-C6alkyl and C1-C6halogenated, and R8selected from the group comprising hydrogen, methyl and ethyl.

15. Connection by claim 11, in which R5denotes a 2,5-disubstituted phenyl.

16. The connection indicated in paragraph 15, in which R5denotes a 2,5-disubstituted phenyl and the substituents are independently selected from the group comprising halogen, cyano, C1-C6alkyl, C1-C6alkenyl,3-C8cycloalkyl, C1-C6halogenated, C1-C6alkoxygroup, C1-C6allylthiourea.

17. Connection P16, inwhich R 1selected from the group comprising halogen, methyl, ethyl, R3and R7denote hydrogen, R5denotes a 2,5-disubstituted phenyl and the Deputy selected from the group comprising halogen, cyano, C1-C6alkyl and C1-C6halogenated, and R8selected from the group comprising hydrogen, methyl and ethyl.

18. Connection by claim 11, in which R5denotes a 3,5-disubstituted phenyl.

19. Connection p, in which R5denotes a 3,5-disubstituted phenyl and the substituents are independently selected from the group comprising halogen, cyano, C1-C6alkyl, C1-C6alkenyl,3-C8cycloalkyl, C1-C6halogenated, C1-C6alkoxygroup, C1-C6allylthiourea.

20. The connection according to claim 19, in which R1selected from the group comprising halogen, methyl, ethyl, R3and R7denote hydrogen, R5denotes a 3,5-disubstituted phenyl and the Deputy selected from the group comprising halogen, cyano, C1-C6alkyl and C1-C6halogenated, and R8selected from the group comprising hydrogen, methyl and ethyl.

21. Connection claim 20 of the formula Ia, in which

R1selected from the group comprising fluorine, chlorine, bromine and methyl;

R8selected from the group comprising hydrogen, methyl and ethyl;/p>

R9selected from the group comprising From1-C6alkyl, C3-C8cycloalkyl, C1-C6halogenated, halogen and cyano.

22. Connection by claim 11, in which R5denotes a 2,4-disubstituted phenyl.

23. Connection p.22, in which R5denotes a 2,4-disubstituted phenyl and the substituents are independently selected from the group comprising halogen, cyano, C1-C6alkyl, C1-C6alkenyl,3-C8cycloalkyl,1-C6halogenated, C1-C6alkoxygroup, C1-C6allylthiourea.

24. Connection item 23, in which R1selected from the group comprising halogen, methyl, ethyl, R3and R7denote hydrogen, R5denotes a 2,4-disubstituted phenyl and the Deputy selected from the group comprising halogen, cyano, C1-C6alkyl and C1-C6halogenated, and R8selected from the group comprising hydrogen, methyl and ethyl.

25. Connection by claim 11, in which R5denotes a 2,6-disubstituted phenyl.

26. Connection A.25, in which R5denotes a 2,6-disubstituted phenyl and the substituents are independently selected from the group comprising halogen, cyano, C1-C6alkyl, C1-C6alkenyl,3-C8cycloalkyl, C1-C6halogenated, C1-C6alkoxygroup, C1-C6/sub> allylthiourea.

27. Connection p, in which R1selected from the group comprising halogen, methyl, ethyl, R3and R7denote hydrogen, R5denotes a 2,6-disubstituted phenyl, and Deputy selected from the group comprising halogen, cyano, C1-C6alkyl and C1-C6halogenated, and R8selected from the group comprising hydrogen, methyl and ethyl.

28. Connection by claim 11, in which R5means 2,3,5-triple-substituted phenyl.

29. The connection of claim 1, wherein X1indicates OR5or SR5; R3and R4selected from the group comprising hydrogen, chlorine, fluorine and methyl; R5denotes optionally substituted pyridinyl, pyridine-N-oxide, indole, quinoline, quinoline-N-oxide.

30. The compound according to claim 1, in which R1and R2together with the carbon atoms to which they are attached, form dihydrofuran or furan ring.

31. The connection of claim 1, wherein X1indicates OR5or SR5; R3and R7denote hydrogen; R4denotes hydrogen or fluorine; R8denotes hydrogen or methyl; and R5denotes optionally substituted phenyl.

32. Pharmaceutical composition comprising a therapeutically effective amount of the compounds of formula I

in which X1selected from the group, who with R 5O, R5S(O)n, R5CH2, R5CH2Oh, R5CH2S(O)n, R5OCH2, R5S(O)nCH2;

R1and R2mean

(i) the substituents, independently selected from the group comprising hydrogen, C1-C6alkyl, C1-C6halogenated,3-C8cycloalkyl,1-C6alkoxygroup, C1-C6allylthiourea, halogen, amino, C1-C6alkylamino, C1-C6dialkylamino, the nitro-group and cyano; or

(ii) taken together represent-CH=CH-CH=CH-, or

(iii) taken together with the carbon atoms to which they are attached, form a 5-membered heteroaromatic or heterocyclic ring containing 1 heteroatom independently selected from O and S;

R3selected from the group comprising hydrogen, halogen, the nitro-group and cyano;

R4selected from the group comprising hydrogen, C1-C6alkyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup,1-C6allylthiourea, halogen, amino, C1-C6alkylamino, C1-C6dialkylamino, aminoacyl, nitro-group and cyano;

R5selected from the group comprising C1-C6alkyl, C3-C 8cycloalkyl, phenyl, naphthyl, pyridinyl, pyridine-N-oxide, indole, quinoline, quinoline-N-oxide; where mentioned phenyl, naftalina, pyridinoline, pyridine-N-oxide, indole, quinoline, quinoline-N-oxide group optionally contain from 1 to 3 substituents independently selected from the group comprising C1-C6alkyl, C1-C6alkenyl, C1-C6halogenated,3-C8cycloalkyl, C1-C6alkoxygroup, C1-C6allylthiourea,1-C6alkylsulfonyl, C1-C6alkylsulfonyl, hydroxy-group, halogen, an amino group, a C1-C6alkylamino, C1-C6dialkylamino, carbarnoyl, the nitro-group and cyano;

R7and R8independently selected from the group comprising hydrogen, an amino group, a C1-C6alkylamino, C1-C6dialkylamino and C1-C6alkyl, optionally containing 1 or 2 substituent, independently selected from the group comprising a hydroxy-group and halogen;

n denotes a whole number equal to from 0 to 2; and

it hydrates, solvate, and salts with acids,

in a mixture with at least one pharmaceutically acceptable carrier or diluent, which when introduced in single or multiple doses adequate for the treatment of diseases mediated VI is the condition of human immunodeficiency HIV.

33. The compound according to any one of claims 1 to 31, with inhibitory activity against reverse transcriptase.



 

Same patents:

FIELD: medicine; pharmacology.

SUBSTANCE: compounds of this invention possess properties of protein kinase inhibitors. In the general formula p means integer within 0 to 2; R and R1 mean O; A1 and A2 mean single bond, (C1-C6)alkyl; B2 means monocyclic or bicyclic, saturated or unsaturated heterocyclic radical including 1 to several identical or different heteroatoms, chosen among O, S, N and NR7, probably substituted with one or several identical or different substitutes.

EFFECT: inhibiting effect on protein kinase, effective application of compounds of formula for medical products.

49 cl, 1 tbl, 6 dwg, 334 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new method of obtaining phenylamide 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxotetrahydropyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid (I), of the key intermediate compound in the synthesis of atorvastatin calcium, which is a hypolipidemic and/or hypocholesteremic agent. The invention also relates to methods of obtaining intermediate product and to new intermediate products.

EFFECT: perfected method of obtaining phenylamide 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxotetrahydropyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid.

11 cl, 3 ex

FIELD: chemistry; medicine.

SUBSTANCE: invention concerns aryl- or heteroarylcarbonylpiperazine compound of the general formula (I) , where R1 is selected out of the group including fluorene-9-on, isoxazole, cinnoline, isothiazole, isoquinoline, 9H-fluorene, 9H-xanthene and 1H-pyrazole, where linkage is implemented by any desired and possible end atom of heteroaryl or aryl radical, so that they can optionally be unsubstituted or mono- or disubstituted by substitutes: halogen, SO2-alkyl, saturated alkyl, non-saturated alkyl with one double link, halogenalkyl where alkyl part contains 1 to 20 carbon atoms, phenyl optionally mono- or disubstituted by substitutes: NO2, -OH, -NH2, halogen; R2 is O; R3 is H; R4 is phenyl substituted by one or two substitutes selected out of group: OH, halogen, alkyl, alkoxy, where alkyl part contains 1 to 20 carbon atoms; or 5, 6 or 7-atom cyclic aromatic radical including N heteroatom and substituted by alkyl containing 1 to 20 carbon atoms; m and n are 1; or its physiologically acceptable salt. The invention also concerns method of obtaining compound of the formula (I), application of compounds of the formula (I) as therapeutically effective compounds for obtaining medication for human and animal tumour treatment, medical preparations based on compound of the formula (I), method of obtaining medications and method of benignant and malignant tumour treatment. The compounds inhibit tubulin polymerisation, thus enabling their application for indicated purpose.

EFFECT: improved efficiency.

15 cl, 2 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: tricyclic bonds are substituted with heterocyclic ones, which have the formula (I), or its pharmaceutically acceptable salt or solvate in which: n denotes 0-2; Q denotes , R1 denotes H, R2 represents H or alkyl with 1-6 carbon atoms, R3 represents H, hydroxy-group, -NR22R23, Het denotes mono- or bycyclic heteroaryl group from 5 - 10 atoms, containing from 1 to 9 carbon atoms and 1 heteroatom N, where Het bonds with B through the cyclic carbon atom, and the group Het has a substitute W. W consists of from 1 to 4 substitutes, independently selected from the group containing H, halogen, R21-aryl and P21-heteroaryl, R4 and R5 are independently selected from the group containing H and alkyl with 1 - 6 carbon atoms, R7, R8, R10 and R11 denote R1, R9 represent H, B represents -(CH2)n3-. cis- or trans -(CH2)n4CR12=CR12a(CH2)n5 or -(CH2)n4C=C(CH2)n5, where n3 denotes 0-5, n4 and n5 independently denote 0-2, and R12 and R12a denote H, X represents -O-, Y represents =O, each R13 is independently selected from the group containing H, alkyl with 1-6 carbon atoms, -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, and -(CH2)n6C(O)NR28R29, where n6 denotes 0, each R14 is independently selected from the group containing H, alkyl with 1-6 carbon atoms, -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16 and -(CH2)n6C(O)NR28R29, where n6 denotes 0, where, at least one of R13 and R14 is chosen from the group containing -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16 and -(CH2)n6C(O)NR28R29, where n6 denotes 0, R16 represents an alkyl with 1-6 carbon atoms, R16b represents H, an alkyl with 1-6 carbonatoms, (an alkoxy with 1-6 carbon atoms)-(an alkyl with 1 - 6 carbon atoms)-, R22-O-C(O)-(an alkyl with 1 - 6 carbon atoms)-, a cycloalkyl with 3-6 carbon atoms, R21 represents from 1 to 3 substitutes, which are independently selected from a group comprising of H, -CN, -CF3, halogen, alkyl with 1 - 6 carbon atoms, -OH, alkoxy- group with 1 - 6 carbon atoms, -C(O)NR25R26 and -SR13, R22 represents H or an alkyl with 1-6 carbon atoms, R23 represents H, R25 and R26 are independently selected from a group comprising of H and an alkyl with 1 - 6 carbon atoms, and R28 and R29 are independently selected from a group comprising of H, an alkyl with 1 - 6 carbon atoms, heteroaryl, heterocyclil and also a pharmaceutical composition, containing these bonds.

EFFECT: application for getting medication for the treatment of diseases related to thrombosis, atherosclerosis, restenosis, hypertension, sternocardia, arrythmia, cardiac insufficiency and cancer, the way of administering is specified in the bonds Also therapy in combination with other cardiovascular agents is allowed.

23 cl, 7 tbl, 92 ex

FIELD: chemistry.

SUBSTANCE: description is given benzimidazole derivatives with general formula I , where Z is chosen from O=; R1 is chosen from C1-10alkyl, R5 R6 N-C1-6alkyl, R5O-C1-6alkyl, R5C(=O)N(-R6)-C1-6alkyl, C3-10cycloalkyl-C1-6alkyl, C3-6heterocycloalkyl-C1-6alkyl C3-6heterocyclyl-C(=O)-C1-6alkyl, C1-10hydrocarbylamino, R5R6N-, R5O-, R5C(=O)N(-R6)-, R5R6NC(=O)N(-R7)-, C3-10cycloalkyl, C3-6heterocyclyl and C3-6heterocyclyl-C(=O)-; R2 is chosen from a group consisting of C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6 alkyl, C3-6heterocycloalkyl-C1-6alkyl, R5R6N- and C3-6heterocycloalkyl; R3 and R4 are independently chosen from -H, -OH, R and -0-R , where R3 and R4 simultaneously do not represent -H. The indicated C1-6alkyl or bivalent C1-6group in definition of R8 are possibly substituted with one or more groups, chosen from halogen, methoxy, ethoxy, hydroxy and -NR5R6; or R3 and R4 together with the nitrogen atom to which they are bonded, form part of a 5- or 6-member ring. The indicated ring is possibly substituted with one or more groups, chosen from methyl, ethyl, halogen, methoxy, ethoxy, hydroxyl and -NR5R. Description is given of a method of obtaining an intermediate product, as well as pharmaceutical compositions, containing formula I compounds.

EFFECT: proposed benzimidazoles relate to therapeutic compounds, which are ligands of receptor CB1 and can be used in making pain killers.

11 cl, 23 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to non-peptide antagonists GnRH, with general formula 1 , where each of A1, A2 and A3 are independently chosen from A5 and A6; and A4 represents either a covalent bond, or A5; under the condition that, if A4 is a covalent bond, then one of A1-A3 represent A6, and the other two represent A5, and that, if A4 represents A5, then all of A1-A3 represent A5; A5 is chosen from C-R13 and N; A6 is chosen from N-R14, S and O; R1 is chosen from H, NHY1 and COY2, and R2 represents H; or and R1, and R2 represents methyl or together represent =O; each of R3, R4 and R5 independently represents H or low alkyl; each of R6, R7, R8, R9, R10, R11 and R12 are independently chosen from H, NH2, F, CI, Br, O-alkyl and CH2NMe2; R13 is chosen from H, F, CI, Br, NO2, NH2, OH, Me, Et, OMe and NMe2; R14 is chosen from H, methyl and ethyl; W is chosen from CH and N; X is chosen from CH2, O and NH; Y1 is chosen from CO-low alkyl, CO(CH2)bY3, CO(CH2)bCOY3 and CO(CH2)bNHCOY3; Y2 is chosen from OR15, NRI6R17 and NH(CH2)cCOY3; Y3 is chosen from alkyl, OR15 and NR16R17; R15 represents H; each of R16 and R17 is independently chosen from H, low alkyl and (CH2)aR18, or together represent -(CH2)2-Z-(CH2)2-; R18 is chosen from OH, pyridyl, pyrizinyl and oxadiazolyl; Z represents NH; a represents 0-4; and b and c represent 1-3. The invention also relates to use of formula 1 a compound as a therapeutic agent and pharmaceutical composition, with antagonistic effect to GnRH receptor. Description is also given of the method of obtaining compounds with the given formula.

EFFECT: obtaining new compounds, with useful biological properties.

27 cl, 70 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the novel indole derivatives with the common formula I: or its pharmaceutically acceptable salt, where R1 is (a) -X-aryl-Y-Z and (b) -X-heteroaryl-Y-Z, where aryl and heteroaryl are unsubstituted or substituted with 1-3 groups, chosen independently from A; aryl means phenyl or naphthyl; heteroaryl means the monocyclic or condensed bicyclic aromatic ring structure containing one heteroatom chosen independently from N or O, where the monocyclic ring or each ring of the bicyclic ring structure means the penta- or hexamerous ring; X means the bond CH2, CH(CH3) and C(CH3)2; Y means -CH=CH-, -CH(OH)CH(OH)-, -OCR7R8-, -SCR7R8- and -CH2CR5R6-; Z means -CO2H, tetrazole; A means C1-4alkyl, -OC1-4alkyl and halogen, where alkyl, and -Oalkyl, each not necessarily substituted with 1-5 halogens; R5, R6, R7 and R8 , each independently means H, C1-C5alkyl, -OC1-C5alkyl, C3-6cycloalkyl and phenyl, where C1-C5alkyl, -OC1-C5alkyl, C3-6cycloalkyl and phenyl are not necessarily substituted with 1-5 halogens; and C3-6cycloalkyl and phenyl are additionally not necessarily substituted with 1-3 groups, independently chosen from C1-C3alkyl and -OC1-C3alkyl, at that, the said C1-C3alkyl and -OC1-C3alkyl are not necessarily substituted with 1-3 halogens; or alternatively, R7 and R8 together can form the C3-C6cycloalkyl group; or alternatively, when R1 means -X-phenyl-Y-Z, Y means -OCR7R8 and R7 are chosen from group containing H, C1-C5alkyl, -OC1-C5alkyl, then R8 can, not necessarily , mean the 1-2-hydrocarbon bridge, bound to the phenylic ring by the orthoposition relative to Y, and generating in this way the 5- or 6-membered heterocyclic ring, condensated with the phenylic ring; R2 means C1-C4alkyl, which is not necessarily substituted with 1-5 halogens; R3 means (a) bensoxazolil, (d) aryl, (e) -C(=O)aryl, (f) -C(=O)heteroaryl, (g) -Oaryl, (i) -S(O)naryl and where R3 is not necessarily substituted with 1-3 substituting groups, independently chosen from halogen, C1-3alkyl, -OC1-3alkyl and -SC1-3alkyl, where C1-3alkyl, -OC1-3alkyl and -SC1-3alkyl are not necessarily substituted with 1-5 halogens; each R4 means from H, halogen, C1-C5alkyl and -OC1-C5alkyl, where C1-C5alkyl and -OC1-C5alkyl are not necessarily substituted with 1-5 halogens; n is the even number 0-2 and p is the even number 1-3.

EFFECT: composition I reveals agonistic activity considering PPAR, that allows to use them in pharmaceutical composition, in means to fix PPAR and production of medication to fix PPAR.

33 cl, 8 tbl, 32 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new substituted 2-(1,2,4-triazole-1-ylmethyl)-6-benzylidene-1,4-dioxaspiro[4.5]decanes represented by the formula I: where R1, R=H, Hal etc., m, n=0-5, and with the process of their production involving condensation of substituted 2-benzylidene cyclohexanone II with 3-halogen-1,3-propanediol by acid catalysis with azeotropic distillation of water in organic dissolvent. Substituted 2-halogenmethyl-6-benzylidene-1,4-dioxaspiro[4.5]decanes represented by the formula III are obtained and further alkylated by 1,2,4-triazolates of alkali metals in polar aprotic dissolvent agent at the temperature of 60 to 180°C. . The invention also concerns fungicide composition containing substituted 2- (1,2,4-triazole-1-ylmethyl)-6-benzylidene-1,4-dioxaspiro[4.5]decanes represented by the formula I, e.g., 2-(1,2,4-triazole-1-ylmethyl)-6-(4-chlorobenzylidene)-10-methyl-1,4-dioxaspiro[4.5]decane oxalate, which possesses higher fungitoxicity than standard triadimephon.

EFFECT: simplifies production and increases output.

3 cl, 1 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention refers to benzamide 4-(phenyl-piperazin-methyl) derivatives of the general formula I in which R1 - aryl, heteroaryl, selected from the group which includes difuryl, pyridyl and thienyl; R2 - hydrogen or C1-12 alkyl. The methods of preparation of the compounds, pharmaceutical composition on their basis and application while preparing medicines are described.

EFFECT: compounds can be applied to treatment of pain and functional gastroenteric upset.

8 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: description is given of the substituted pyridine with formula in which the substituting groups have values given in paragraph 1 of the formula of invention. Description is also given of the herbicide compound on its base and the derived pyridine of formula , in which the substituting groups have values given in paragraph 4 of the formula of invention, which is an intermediate product.

EFFECT: compounds have an herbicide action.

5 cl, 24 tbl, ex

FIELD: chemistry.

SUBSTANCE: in general formula (I) , R1 represents similar or different 2 groups, each of which is selected from group consisting of C1-3alkyl, or when R1 are two adjacent groups, two groups R1, taken together, can form saturated or unsaturated 5- or 6-member cyclic group, which can have 1 or 2 oxygens as heteroatom; X represents oxygen or sulphur; values of other radicals are given in invention formula.

EFFECT: increase of composition efficiency.

16 cl, 11 tbl, 31 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to compounds of formula (I) or their pharmaceutically acceptable salts, where Q represents optionally substituted with 1-3 substituents, determined in formula, phenyl or pyridyl or pyrodazinyl; R2 represents C1-6alkyl or aminogroup, determined in item 1 of formula or C1-6alkyl, substituted with said aminogroup; bond between oxygen atom O* and adjacent carbon atom C1 or (i) is double bond, which determines carbonyl group [C(=O)], where R6 represents C1-6alkyl or cyclopropyl; or (ii) represents simple bond, where, in case of simple bond, said oxygen atom O*, is in addition bound to group R6 and, taken together with R6 and with adjacent nitrogen atom, determines optionally substituted with C1-6alkyl, oxadiazolyl ring, bond between C1 and adjacent nitrogen atom being double bond.

EFFECT: obtaining medications which are useful in obtaining medications for treatment of conditions connected with p38 kinase and/or in obtaining medications for treatment of inflammatory diseases or conditions in patient.

8 cl, 6 tbl, 88 ex

FIELD: chemistry.

SUBSTANCE: obtaining optically active 5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl)-1H-benzo[d]imidazole, demonstrating anti-ulcer activity, by enantioselective oxidation by organic proxides of 5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methyltio)-1H-benzo[d]imidazole in presence of catalyst in organic solvent, as catalyst, preliminary obtained in situ complex of vanadium salt with chiral Shiff base, described by general formulas III and IV, , is used, substituents R1, R2, R3, R4 can be similar or different and can be hydrogen atom, alkyl group (including ones which contain halogen atoms), alkyloxy group (including ones containing halogen atoms), nirtogroup, dialkylamino group, halogen; R5 is optically active substituent; reaction is carried out at reduced temperature with possible presence of organic base with further product isolation by usual methods.

EFFECT: novel compounds possess useful biological properties.

1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: method lies in enantioselective oxidation with organic peroxides of (S)-5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-benzo[d]imidazole in presence of catalytic complex of titanium (IV) with simultaneously two chiral ligands: chiral diol (preferably D-diethyltartrate) and chiral amine (preferably N,N-dimethyl-(R)-1-phenylethylamin).

EFFECT: increase of target product or its salt output.

1 cl, 1 dwg, 4 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) HetAr represents pyrimidinyl or thiadiasolyl; R1 and R2 represent H; A represents C1-C2-alkyl; B represents aryl(CH2)0-3-O-C(O)-or arylcyclopropyl-C(O)-, in which aryl can be substituted with 1-5 substituents, each substituent represents C1-C4-alkyl. Invention also relates to pharmaceutical composition and to application of compounds of item 1. Obtaining novel compounds, as well as pharmaceutical composition possessing NMDA/NR2B antagonist activity.

EFFECT: increase of composition efficiency.

13 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: compounds of formula (I) can be efficient with respect to diseases, in which phosphorylation of Tau protein takes place. , R3 stands for CONR1R2, where R1 and R2 can be substituted with heterocycle; R5, R6, R7 independently on each other are selected from halogen and phenyl; R1, R2 independently on each other stand for hydrogen, (C1-C6)alkyl or together with nitrogen of group CONR1R can form heterocycle.

EFFECT: obtaining novel biologically active compounds.

4 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) X stands for C, N; R1 stands for H or (lower) alkyl, R2 stands for 9(lower) alkyl, -(CH2)n-R2a; R2a stands for C3-C8cycloalkyl, optionally and independently mono-, di-, tri- or tetrasubstituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent saturated heterocyclic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heterocyclic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent heteroaromatic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heteroaromatic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, C3-C6cycloalkyl; R3 stands for C3-C6cycloalkyl, being optionally and independently mono-, di- or tri- or tetra-substituted with groups: OH, (lower) alkyl, (lower)alkoxy, phenyl, which optionally and independently is mono-, di- or tri- or tetra-substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; R4 stands for 5- or 6-member single-valent heteroaromatic ring, containing from one to two nitrogen heteroatoms, said heteroaromatic ring being optionally and independently mono-, di- or tri- substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, halogen; naphtyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; or phenyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, nitro, halogenated (lower)alkyl, halogenated (lower)alkoxy, cyano, (lower)alkylsulfonyl, -NR7R8; or two neighbouring substituents in said phenyl residue together represent -O-(CH2)p-O-, -(CH2)2-C(O)NH-; R5 and R6 each independently represent H, (lower)alkyl; R7 and R8 each independently represent hydrogen, (lower)alkyl, or R7 and R8 together with nitrogen atom, to which they are bound, form 5- or 6- member saturated or aromatic heterocyclic ring, which optionally contain nitrogen as additional heteroatom; said saturated or aromatic heterocyclic ring, being optionally substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy; m equals 1 or 2, n equals 0 or 1, p equals 1, 2 or 3; or their pharmaceutically acceptable salts.

EFFECT: increased antagonistic activity of compounds.

19 cl

FIELD: chemistry.

SUBSTANCE: invention pertains to acidylated heteroarylcondensed cycloalkenylamines with formula I in any of their stereoisomeric form or in form of their mixtures in any ratio, or their pharmaceutical salts, where in formula I: ring A represents an aromatic 6-member ring, containing 1 nitrogen atom, or a 5-member aromatic ring, containing 1 sulphur atom; one or two of R1, R2, R3 and R4 is independently chosen from a group consisting of hydrogen, halogen or C1-C4-alkyl, and the other R1, R2, R3 and R4 represent hydrogen; R5 represents an Ar group or Hetar group. Description is also given of a pharmaceutical composition based on compound with formula I and use of the latter.

EFFECT: regulation of the expression of the enzyme endothelial NO-synthesis.

10 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyridinyl carbamates of general formula (I) , where R1 and R2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, amide, urea, thiourea, benzamide, thioamide, halogen, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, amide, urea, thiourea, benzamide, thioamide, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl can be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, thioxo, halogen, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl can be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl ; R3, and R4 are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl can be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl can be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy. Invention also relates to pharmaceutical composition, possessing activity of inhibiting lipolytic activity of hormone-sensitive lipase, which contains compounds of formula (I), to their application for treatment and/or prevention of diseases and disorders, related to hormone-sensitive lipase and to method of their production.

EFFECT: obtaining novel compounds, possessing useful biological properties.

23 cl, 1 tbl, 77 ex

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

SUBSTANCE: invention relates to new derivatives of sulfonamides of the formula (I) or their pharmaceutically acceptable salts wherein R1 means -OH or -NHOH; R2 means hydrogen atom; R3 means alkyl, alkoxyalkyl, arylalkyl, pyridylalkyl or morpholinylalkyl; A means piperidyl or tetrahydrofuranyl; n = 0; E means a covalent bond; (C1-C4)-alkylene, -C(=O)-, -C(=O)O- or -SO2-; X means hydrogen atom, alkyl, aryl, arylalkyl, alkoxyalkyl, morpholinyl or tetrahydropyranyl; each among G and G' means -C(R5)=C(R5') wherein R5 and R5' mean hydrogen atom; M means the group -CH-; z means the group -(CR7R7')a-L-R8 wherein a = 0 and each among R7 and R7' means hydrogen atom; L means a covalent bond; R8 means halogen atom or alkoxy-group. Compounds of the formula (I) are inhibitors of metalloproteases and can be used for treatment of arthritis, cancer tumors and other diseases.

EFFECT: valuable medicinal properties of compounds.

15 cl, 7 tbl, 56 ex

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