Substituted quiinobenzoxazin analogues

FIELD: chemistry.

SUBSTANCE: claimed invention relates to quinobenzoxazin analogues with general formula (1) where V represents H, halo-, or NR1R2; NH2, or NR1-(CR12)n-NR3R4; A represents H, fluoro-, or NR12; Z represents O, S, NR1 or CH2; U represents NR1R2; X represents NR1R2 or halo-; n=1-6; where in NR1R2, R1 and R2 can form 5-7-member heterocyclic ring which is optionally substituted and has 1-2 heteroatoms, selected from group consisting of N, O and S; R1 represents H or C1-6alkyl; R2 represents C1-10alkyl optionally including one or more non-adjacent heteroatoms N or O and is optionally substituted with if necessary substituted 3-6-member carbocyclic or 5-14-member heterocyclic ring; or R2 is 5-14-member heterocyclic ring, which has 1-2 heteroatoms, selected from group consisting of N, O or S, 6-member aryl or 5-7member heteroaryl ring, which contains 1-3 heteroatoms, selected from group consisting of N, O and S, each of which can be, if necessary, substituted; R3 represents H or C1-6alkyl; R4 represents H, C1-6alkyl, optionally substituted with 3-6 carbocyclic or 5-14-member heterocyclic ring, or 6-member aryl, R4 and R3, if necessary, can form optionally 5-7-member substituted heterocyclic ring, which contains 1-2 heteroatoms selected from N and O; W represents substituent, such as described in i.1 of invention formula, where Q, Q1, Q2, and Q3 represents independently CH or N; Y represents independently O or CH; R5 represents substituent in any position of closed ring in form of H or OR2; on condition that U is not morpholinyl or 2,4-difluoroaniline, when X represents F or pyrrolidinyl, A is F, Z represents O, and W represents phenylene; each obligatorily substituted fragment being substituted with one or more halogen, C1-6-alkoxy, amino, carbamate, C1-10alkyl, C2-10alkenyl, each of which is optionally substituted with halogen, =O, 6-member aryl or one or more heteroatom, selected from N and O; 6-member aryl, 3-6-member carbocyclic ring or 5-7-member heterocyclic ring containing 1-2 heteroatoms, selected from group, consisting of N and O; or its pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition based on formula (1) compound and to method of treatment of proliferative cell diseases using formula (1) compounds.

EFFECT: obtaining novel quinobenzoxazin analogues possessing useful biological properties.

48 cl, 3 tbl, 50 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (1)

where V represents H, halo, or NR1R2; NH2or NR1-(CR12)n-NR3R4;
And denotes H, fluorescent-, or NR12;
Z represents O, S, NR1or CH2;
U denotes NR1R2;
X represents NR1R2or halo;
n=1-6;
where NR1R2, R1and R2can form a 5-7 membered heterocyclic ring which is optionally substituted and has 1 to 2 heteroatoms selected from the group consisting of N, O and S;
R1denotes N or C1-6alkyl;
R2stands With1-10alkyl, optionally comprising one or more nonadjacent heteroatoms N or O and is optionally substituted by an optionally substituted 3-6-membered carbocyclic or 5 to 14-membered heterocyclic ring; or R2is a 5-14-membered heterocyclic ring which has 1 to 2 heteroatoms selected from the group consisting of N, O or S, a 6 membered aryl or a 5-7 membered heteroaryl ring which contains 1-3 heteroatoms selected from the group consisting of N, O and S, which each of which may be optionally substituted;
R3denotes N or C1-6alkyl;
R4denotes H, C1-6alkyl, optionally substituted 3-6-membered carbocyclic or 5 to 14-membered heterocyclic ring, or 6-membered aryl, and R3and R4if necessary, can be optional form a 5-7 membered substituted heterocyclic ring containing 1-2 heteroatoms selected from N and O;
W denotes a Deputy chosen from the group:







where Q, Q1, Q2and Q3means independently CH or N;
Y represents independently O or CH;
R5means a substituent in any position closed ring in the form N or or2;
provided that U is not what morpholinium or 2,4-diftorhinolonom, when X represents F or pyrrolidinyl, And is F, Z denotes O, and W stands for a phenylene;
each necessarily substituted fragment is substituted by one or more halogen, C1-6-alkoxy, amino, carbamate,1-10the alkyl, C2-10alkenyl, each of which is optionally substituted with halogen, =O, 6-membered aryl or one or more heteroatom selected from N and O; 6-membered aryl, 3-6-membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-2 heteroatoms selected from the group consisting of N and O;
or its pharmaceutically suitable salts.

2. The compound according to claim 1, where a and X are independently fluorine.

3. The compound according to claim 2, where a represents fluorine.

4. The compound according to claim 1, where V represents N.

5. The compound according to claim 1, where U and X are independently mean NR1R2.

6. The compound according to claim 5, where R1is H, a R2means1-10alkyl, optionally containing one or more nonadjacent heteroatoms N or O and optionally substituted by an optionally substituted C3-6cycloalkyl, 6-membered aryl or a 5-14-membered heterocyclic ring containing 1-3 heteroatom selected from the group consisting of N, O or S.

7. The connection according to claim 6, where the mentioned 5-14-membered heterocyclic ring is selected from the group of tetrahydrofuran, 1,3-dioxolane, 2,3-digidrive the Academy of Sciences, tetrahydropyran, benzofuran, isobenzofuran, 1,3-dihydroisobenzofuran, isoxazol, 4,5-dihydroisoxazole, piperidine, pyrrolidine, pyrrolidin-2-it, pyrrole, pyridine, pyrimidine, octahedral[3,4-b]pyridine, piperazine, pyrazin, morpholine, thiomorpholine, imidazole, imidazolidine-2,4-dione, benzimidazole, 1,3-dehydrobenzperidol-2-it, indole, thiazole, benzothiazole, thiadiazole, thiophene, tetrahydrothiophene-1,1-dioxide, diazepin, triazole, guanidine, diazabicyclo[2.2.1]heptane, 2,5-diazabicyclo[2.2.1]heptane and 2,3,4,4A,9,9a-hexadiyne-1H-β-carbolin.

8. The compound according to claim 5, where R1is H, a R2mean 6-membered aryl or a 5-14-membered heterocyclic ring containing 1-3 heteroatom selected from the group consisting of N, O or S, each of which is optionally substituted with amine or another 5-7-membered heterocyclic ring containing 1-2 heteroatoms selected from the group consisting of O and N.

9. The compound of claim 8 where the above-mentioned 5-14-membered heterocyclic ring is selected from the group of tetrahydrofuran, 1,3-dioxolane, 2,3-dihydrofuran, tetrahydropyran, benzofuran, isobenzofuran, 1,3-dihydroisobenzofuran, isoxazol, 4,5-dihydroisoxazole, piperidine, pyrrolidine, pyrrolidin-2-it, pyrrole, pyridine, pyrimidine, octahedral[3,4-b]pyridine, piperazine, pyrazin, morpholine, thiomorpholine, imidazole, imidazolidine-2,4-dione, benzimidazole, 1,3-dihydrobenzo idazole-2-it, indole, thiazole, benzothiazole, thiadiazole, thiophene, tetrahydrothiophene-1,1-dioxide, diazepin, triazole, guanidine, diazabicyclo[2.2.1]heptane, 2,5-diazabicyclo[2.2.1]heptane and 2,3,4,4A,9,9a-hexahydro-1H-β-carbolin.

10. The compound according to claim 5, where R1and R2in NR1R2form a substituted or unsubstituted 5-7-membered heterocyclic ring containing 1-2 heteroatoms selected from the group consisting of N, O or S.

11. The connection of claim 10, where NR1R2means morpholine, thiomorpholine, piperazine, piperidine or diazepino, each of which is optionally substituted.

12. The compound according to claim 1, where U and X are independently have the formula

where R1and R3means independently N or C1-6alkyl;
n=1-6;
R4denotes N or C1-6alkyl, optionally substituted 3-6-membered carbocyclic or 5 to 14-membered heterocyclic ring;
and where NR3R4R3and R4can form a substituted or unsubstituted 5-7-membered heterocyclic ring which has 1 to 2 heteroatoms selected from the group consisting of O and N.

13. The connection section 12, where n is 2-3.

14. The connection section 12, where NR3R4means acyclic amine or guanidine, or tautomer; or R3and R4optionally form a substituted 5-7-membered heterocyclic Kohl is about, which has 1 to 2 heteroatoms selected from the group consisting of N and O.

15. The connection section 12, where NR3R4means morpholine, imidazole, pyrrolidine, piperazine, pyridine or piperidine, each of which is optionally substituted.

16. The compound according to claim 1, where X represents NR1R2a U has the formula

where R1and R2means as defined in claim 1;
R3denotes N or C1-6alkyl;
n=1-6;
R4denotes N or C1-6alkyl, optionally substituted 3-6-membered carbocyclic or 5 to 14-membered heterocyclic ring which has 1 to 2 heteroatoms selected from the group consisting of O and N;
and where R1and R2in NR1R2, a R3and R4in NR3R4each independently may form a substituted 5-7-membered heterocyclic ring which has 1 to 2 heteroatoms selected from the group consisting of N and O.

17. Connection P16, where R1and R2in NR1R2, a R3and R4in NR3R4each independently form a substituted 5-7-membered heterocyclic ring containing 1-2 heteroatoms selected from the group consisting of N and O.

18. The connection 17, where X is substituted or not substituted amine, carbamate,1-10the alkyl containing one or more nonadjacent atoms N, O or S, and alseny or unsubstituted 5-7-membered heterocyclic ring, 6-membered aryl or saturated or not saturated 5-7 membered heterocyclic ring, each of which are optionally substituted.

19. The connection 17, where X is substituted heterocyclic ring, selected from the group of tetrahydrofuran, 1,3-dioxolane, 2,3-dihydrofuran, tetrahydropyran, benzofuran, isobenzofuran, 1,3-dihydroisobenzofuran, isoxazol, 4,5-dihydroisoxazole, piperidine, pyrrolidine, pyrrolidin-2-it, pyrrole, pyridine, pyrimidine, octahedral[3,4-b]pyridine, piperazine, pyrazin, morpholine, thiomorpholine, imidazole, imidazolidine-2,4-dione, benzimidazole, 1,3-dehydrobenzperidol-2-it, indole, thiazole, benzothiazole, thiadiazole, thiophene, the tetrahydrothiophene-1,1-dioxide, diazepin, triazole, guanidine, diazabicyclo[2.2.1]heptane, 2,5-diazabicyclo[2.2.1]heptane and 2,3,4,4A,9,9a-hexahydro-1H-β-carbolin.

20. The connection 17, where X and NR3R4means independently morpholine, imidazole, pyrrolidine, piperazine, pyridine or piperidine, each of which is optionally substituted.

21. Connection claim 20, where X and NR3R4independently mean pyrrolidine, each of which is optionally substituted.

22. Connection item 21, where X is replaced by pyrazino.

23. Connection p.22, where W means naphthalenyl.

24. The compound according to claim 1, where W stands for a benzene, pyridine, diphenyl, naphthalene, phenanthrene, quinoline, isoquinoline, hinzelin, inulin, phthalazine, cinoxacin, indole, benzimidazole, benzoxazole, benzthiazole, benzofuran, Andron, xanthone, acridan, fluorene, carbazole, pyrimido[4,3-b]furan, pyrido[4,3-b]indole, pyrido[2,3-b]indole, dibenzofuran, acridine or acridity.

25. The compound according to claim 1, where the specified connection manifests chiral properties.

26. Pharmaceutical composition useful for reducing cell proliferation or inducing cell death, comprising the compound according to claim 1 and a pharmaceutically acceptable filler.

27. A method of treating cell proliferative diseases comprising administration to the subject effective amounts of compounds according to claim 1 or a pharmaceutical composition, resulting cured above proliferative cell disease.

28. The method according to item 27, in which the aforementioned cell proliferative disease is cancer.

29. The method according to item 27, which suppressed cell proliferation or cell death is induced.

30. The method according to item 27 in which the said subject is a human or an animal.

31. The method of inhibition of cell proliferation or inducing cell death, comprising contacting the system with an effective amount of a compound according to claim 1 or a pharmaceutical composition, leads to the inhibition of cell proliferation or induction of cell death in the above is the system.

32. The method according to p where the above-mentioned system is a cell or tissue.

33. A method of reducing microbial titers, comprising contacting the system with an effective amount of a compound according to claim 1 or a pharmaceutical composition, which leads to the reduction of microbial titles.

34. The method according to p, where the system is a cell or tissue.

35. The method according to p in which microbial titles are the titles of viruses, bacteria and fungi.

36. A method of treating a microbial infection, comprising administration to the subject effective amounts of compounds according to claim 1 or a pharmaceutical composition, resulting cured aforementioned microbial infection.

37. The method according to p, in which the said object is a person or an animal.

38. The method according to p, where the microbial infection is a viral, bacterial or fungal infection.

39. The compound according to claim 1, where V denotes NH2or NR1-(CR12)n-NR3R4,
where R1and R3are independently N or C1-6alkyl;
n=1-6;
R4means H, C1-6alkyl, substituted or unsubstituted 3-6 membered carbocyclic or 5-7 membered heterocyclic ring which has 1 to 2 heteroatoms selected from the group consisting of O and N or 6-clenney aryl; and where may form optionally substituted 5-7-membered, heterocy the symbolic ring, which has 1 to 2 heteroatoms selected from the group consisting of O and N.

40. Connection P16, where V denotes N.

41. Connection P16, where a means of fluorescent.

42. Connection P16, where W means naphthalenyl.

43. Connection item 23, where V denotes N, and a fluorescent.

44. The compound according to claim 1, where the specified connection is selected from the compounds presented in table 2.

45. The compound according to claim 1, where Z means Acting

46. The compound according to claim 1, where the compound is chosen from the group consisting of compounds 339, 356, 468, 469, 494 516 presented in table 2.

47. Connection p.46, where connection is the connection 516 presented in table 2.

48. Connection p.46, where connection is the connection 494 presented in table 2.



 

Same patents:

FIELD: chemistry.

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EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases.

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35 cl, 3 tbl, 147 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry.

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EFFECT: obtaining new biologically active compounds and a medicinal composition, based on these compounds, which is a sodium channel inhibitor.

10 cl, 91 ex, 22 tbl

FIELD: chemistry.

SUBSTANCE: invention claims compound of the general formula (I) , where R is hydrogen atom or vinyl group; n is 1, X is a group of the formula CH or nitrogen atom, R1 is either phenyl or naphthyl group, or cyclohexyl group, or heteroaryl group, R2 is either hydrogen atom or one or more substitutes selected out of halogen atoms and trifluoromethyl, alkyl, alkoxyl phenyloxy, hydroxyl groups or group of the general formula -NR4R5, SO2NR4R5, or group of the formula -OCF2O-, each of R4 and R5 groups is hydrogen atom or alkyl group; and method of obtaining compound of the general formula (I), medicine, pharmaceutical composition. Compounds display special effect as specific inhibitors of glycine GlyT1 and/or GlyT2 transmitters and thus are applied in treatment of various diseases.

EFFECT: obtaining compounds with high specific inhibition effect.

13 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: derivatives of 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene of general formula I , general formula I, where X and W or both represent -CH-, or one of them represents -CH-, and the other -N. V represents -A-(CH2)s-, -(CH2)s-A-, -A-(CH2)v-B- or -CH2-A-(CH2)3-B-; A and B represent-O- U -phenyl, possibly 1-3 substituted with halogen, alkyl, alkoxy, CF3, CF3O - or alkylcarbonyl, or pyridyl, monosubstituted with cyanogroup. T represents -CONR1-, -(CH2)pOCO- or -(CH2)pN(R1)CO- Q-alkylene; M - hydrogen, phenyl, possibly substituted, benzo[1,3]dioxol, possibly substituted, or pyridyl; L represents -R3, -COR3, -COOR3, -CONR2R3 or -SO2R3; R1 - hydrogen, alkyl, C3-7 cycloalkyl, pyrrolidinyl, benzo[b]thienyl, chinoxalinyl, phenylalkyl, thienylalkyl or tetrazolylalkyl, possibly substituted. m=1, n=0 or m=0, n=1, p - integer 1-4, s - integer 2-5, v - integer 2-4, optically pure enantiomers, mixtures of enantiomers, pharmaceutically acceptable salts and complexes with solvents, possessing activity of phenin inhibitors.

EFFECT: efficient application in medicine for treatment of cardio-vascular diseases and renal failure.

8 cl, 743 ex

FIELD: chemistry.

SUBSTANCE: description is given of new diazabicyclic aryl derivatives, with general formula I: its enantiomers, or mixture of enantiomers, or its adjoining pharmaceutical salt, where X and Y independently represent CR2, CR3 or N, where R2 is hydrogen, C1-6alkyl or halogen; and R3 is hydrogen or halogen; and R1 is hydrogen or halogen, CF3, NO2 or phenyl, possibly substituted, group with formula phenyl-Z-(C1-6alkyl)m-, phenyl -C≡C- or pyridyl -Z-(C1-6alkyl)m-, where m equals 0 or 1; Z - O or S, where phenyl and pyridyl are possibly substituted, or R1 and R3 , together with carbon atoms to which they are bonded, form a benzocondensed aromatic carbocyclic ring, which can be substituted. The new compounds are cholinergic ligands of nicotinic acetylcholine receptors.

EFFECT: compounds can be useful for treating such diseases or disorders related to the cholinergic system of the central nervous system, peripheral nervous system etc.

11 cl, 3 ex, 1 tbl

FIELD: organic chemistry.

SUBSTANCE: invention relates to novel individual compounds of series 2,5a-methano[1,4]diazepino[1,7-a]-quinoxaline-5-carboxylates, namely, to isopropyl-12-aroyl-2-hydroxy-1,6-dioxo-4-(3-pyridinyl)-7-phenyl-1,3,6,7-tetrahydro-2,5a-methano[1,4]diazepino[1,7-a]-quinoxaline-5-carboxylates of the formula (1) wherein Ar means phenyl or p-methoxyphenyl, and to a method for their synthesis. Method for synthesis of compound of the formula (1) involves interaction of 3-aroyl-5-phenylpyrrolo[1,2-a]-quinoxaline-1,2,4(5H)-triones with isopropyl-3-amino-3-(3-pyridinyl)-2-propenoate in an inert aprotonic solvent medium and the following isolation of end substances. The proposed method provides synthesis of novel compounds of the formula (1) possessing antibacterial effect with high yield and selectivity.

EFFECT: improved method of synthesis.

4 cl, 1 tbl, 3 ex

FIELD: organic chemistry, chemical technology, medicine.

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EFFECT: improved preparing and treatment methods.

33 cl, 69 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to new individual compounds of azapentacycloeicosanes class. Invention describes 20-aroyl-12-hydroxy-17,17-dimethyl-3-phenyl3,10,13-triazapentacyclo[10.7.1.01,10.O4,9.O14,19]eicosa-4,6,14(19)-2,11,15-triones of the formula:

wherein R means hydrogen atom; Ar means phenyl; or R means benzyl and Ar means p-methoxyphenyl group. Also, the invention describes a method for preparing these compounds. Invention provides preparing new compounds that can be used as the parent substances for synthesis of new heterocyclic systems.

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

4 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention claims compound of the general formula (I) , where R is hydrogen atom or vinyl group; n is 1, X is a group of the formula CH or nitrogen atom, R1 is either phenyl or naphthyl group, or cyclohexyl group, or heteroaryl group, R2 is either hydrogen atom or one or more substitutes selected out of halogen atoms and trifluoromethyl, alkyl, alkoxyl phenyloxy, hydroxyl groups or group of the general formula -NR4R5, SO2NR4R5, or group of the formula -OCF2O-, each of R4 and R5 groups is hydrogen atom or alkyl group; and method of obtaining compound of the general formula (I), medicine, pharmaceutical composition. Compounds display special effect as specific inhibitors of glycine GlyT1 and/or GlyT2 transmitters and thus are applied in treatment of various diseases.

EFFECT: obtaining compounds with high specific inhibition effect.

13 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: derivatives of 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene of general formula I , general formula I, where X and W or both represent -CH-, or one of them represents -CH-, and the other -N. V represents -A-(CH2)s-, -(CH2)s-A-, -A-(CH2)v-B- or -CH2-A-(CH2)3-B-; A and B represent-O- U -phenyl, possibly 1-3 substituted with halogen, alkyl, alkoxy, CF3, CF3O - or alkylcarbonyl, or pyridyl, monosubstituted with cyanogroup. T represents -CONR1-, -(CH2)pOCO- or -(CH2)pN(R1)CO- Q-alkylene; M - hydrogen, phenyl, possibly substituted, benzo[1,3]dioxol, possibly substituted, or pyridyl; L represents -R3, -COR3, -COOR3, -CONR2R3 or -SO2R3; R1 - hydrogen, alkyl, C3-7 cycloalkyl, pyrrolidinyl, benzo[b]thienyl, chinoxalinyl, phenylalkyl, thienylalkyl or tetrazolylalkyl, possibly substituted. m=1, n=0 or m=0, n=1, p - integer 1-4, s - integer 2-5, v - integer 2-4, optically pure enantiomers, mixtures of enantiomers, pharmaceutically acceptable salts and complexes with solvents, possessing activity of phenin inhibitors.

EFFECT: efficient application in medicine for treatment of cardio-vascular diseases and renal failure.

8 cl, 743 ex

FIELD: chemistry.

SUBSTANCE: description is given of new diazabicyclic aryl derivatives, with general formula I: its enantiomers, or mixture of enantiomers, or its adjoining pharmaceutical salt, where X and Y independently represent CR2, CR3 or N, where R2 is hydrogen, C1-6alkyl or halogen; and R3 is hydrogen or halogen; and R1 is hydrogen or halogen, CF3, NO2 or phenyl, possibly substituted, group with formula phenyl-Z-(C1-6alkyl)m-, phenyl -C≡C- or pyridyl -Z-(C1-6alkyl)m-, where m equals 0 or 1; Z - O or S, where phenyl and pyridyl are possibly substituted, or R1 and R3 , together with carbon atoms to which they are bonded, form a benzocondensed aromatic carbocyclic ring, which can be substituted. The new compounds are cholinergic ligands of nicotinic acetylcholine receptors.

EFFECT: compounds can be useful for treating such diseases or disorders related to the cholinergic system of the central nervous system, peripheral nervous system etc.

11 cl, 3 ex, 1 tbl

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to new crystalline form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride, including 2 moles water to 1 mole (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride, the form II content being equal 75% and more; the above form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3,3,1]non-4-yl)benzamide hydrochloride has one or more optional properties, as follows: a) form II infrared spectrum include characteristic peak at 835±1.5 cm-1; b) X-ray pattern obtained on the above form powder is essentially corresponds to image Fig. 21; and c) water content rates 8.3% to 9.8%. The invention relates also to the form II ofhydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride production methods, to the form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride, and the form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride identification method, as well as to pharmaceutical composition and treatment method for gastrointestinal motility impairment related disorders.

EFFECT: composition has improved properties for medical applications.

22 cl, 1 ex, 11 tbl, 22 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns new derivatives of 1- and 7-[ω-(benzhydryl-4-piperazinyl-1)alkyl]-3-alkyloxantines of the general formulae I and II, including their pharmaceutically acceptable salts and/or salt hydrates, the derivatives showing antihistaminic and antiallergenic effect. In the general formulae I and II : R = H, Me, CH2Ph; R1 = Me, "н" - C4H9; n = 0-3; X = H, OH, OCOCH2CH2COOH; Y = Y1 = H, Cl, F; on the condition that R and R1 are not both methyl. Compounds of the invention feature high antihistaminic and antiallergenic activity. E.g., 7-[4-(benzhydryl-4-piperazinyl-1)butyl]-3-methyloxantine dihydrochloride surpasses most efficient antihistaminic and antiallergenic medications, such as cetirizine, loratadine and azelastine, in activity and lasting effect.

EFFECT: obtaining a compound with high antihistaminic and antiallergenic activity.

2 cl, 3 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new N,N'-substituted 3,7-diazabicyclo[3.3.1]nonanes of the general formula 1: (HY), where HY is hereinafter a pharmacologically acceptable acid; E is , R1 is H, low-grade alkyl, C1-C10alkoxy; R2 is generally represented by the general formulae (1.1a) , (1.2a) , (1.3a) , (1.4a) , where L is CHR11, ; R11 is H, NH2; R15 is H, low-grade alkyl, C1-C10alkoxy; R19, R19', R20 and R20' can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; R24 and R25 can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; R3 and R3' can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; R4 and R4' can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; X is a group of the general formula: (CH2)m-Z, where m=0, while Z is acetyl, or X is a valence link. Compounds I are capable of AMPA receptor activity modulation and hence can be applied in pharmaceutical compositions.

EFFECT: obtaining compound capable of AMPA receptor activity modulation.

12 cl, 2 dgw, 2 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention concerns malonamide derivatives of the formulae (IA) or (IB) , and pharmaceutically acceptable acid additive salts of them, where R1, R1',(R2)1,2,3, R3, R4, R14, L, and are such as described in this invention. Also the invention concerns a medicine with inhibition effect on γ-secretase, which can be applied in treatment of Alzheimer's disease.

EFFECT: obtaining new malonamide derivatives with beneficial biological properties.

17 cl, 188 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of 1,4-diazabicycloalkane of the formula (IV): or its pharmaceutically acceptable addition salt wherein Ar represents carbocyclic aromatic (aryl) group or heterocyclic aromatic (heteroaryl) group that represents 5-6-membered ring comprising one nitrogen, sulfur or oxygen atom as a heteroatom and wherein aromatic group can be substituted with one substitute chosen from group consisting of (C1-C6)-alkoxy, halogen atom, -CF3, phenyl and benzyl. Also, invention relates to a pharmaceutical composition possessing inhibitory effect on nicotine acetylcholine receptors and containing the effective amount of compound of the formula (IV) or its pharmaceutically acceptable addition salt in combination with at least one pharmaceutically acceptable carrier or diluting agent. Invention provides derivatives of 1,4-diazabicycloalkane possessing inhibitory activity with respect to nicotine acetylcholine receptors.

EFFECT: valuable medicinal and pharmacological properties of compounds.

10 cl, 3 ex

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

SUBSTANCE: invention relates to novel 3-phenyl-3,7-diazabicyclo[3,3,1]nonane compounds of the formula (I): wherein R1 means (C1-C6)-alkyl, (C4-C7)-cycloalkyl; R2 means (lower)-alkyl; R3 means (lower)-alkyl, or R2 and R3 form in common (C3-C6)-alkylene chain; R4 means phenyl monosubstituted at ortho- or para-position with nitro-, cyano-group or (lower)-alkanoyl, or disubstituted at ortho- and para-position with nitro-group, and their physiologically acceptable acid-additive salts. Compounds of the formula (I) possess anti-arrhythmic activity and therefore they can be used in pharmaceutical composition used in treatment and/or prophylaxis of cardiac rhythm disorders. Also, invention describes a method for synthesis of these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

8 cl, 6 tbl, 2 ex

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to condensed heterocyclic succinamide compounds of the formula (I): , their pharmaceutically acceptable salts, solvates or isomers wherein G represents mono- or polycyclic aryl or heterocyclic group substituted possibly at one or more positions; L represents a bond, -(CR7R7')n (wherein n = 1; R7 and R7' represents independently hydrogen atom (H), alkyl or substituted alkyl) or -CH2-NH-; Z1 represents oxygen atom (O); Z2 represents O; A1 and A2 represent -CR7 or in common with R7 from group W is a heterocyclic ring wherein oxygen represents a heteroatom; Y represents -O-, -SO-, -N(V2)-, -CH2-N(V2)-, -CO-N-(alkyl)-, -CH2-S-, -CH2-SO2-; V2 represents hydrogen atom, alkyl, arylalkyl, -CO-alkyl, -CO-O-aryl, -CO-O-arylalkyl; W represents -CR7R7'-CR7R7'-, -CR7R7'-C=O, -NR9-, -CR7R7'-, -N=CR8-, -N=N, -NR9-NR9'-, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo- or substituted heterocyclo-group, aryl or substituted aryl wherein if W doesn't mean -NR9-CR7R7'-, -N=CR8-, -N=N, -NR9-NR9'- or heterocyclo- or substituted heterocyclo-group then Y must mean -O-, -CH2-S-, -SO-, -CH2-SO2-, -N-(V2)- or -CH2-N-(V2)-; Q1 and Q2 represent hydrogen atom (H). Also, invention describes a method for synthesis of intermediate compounds in synthesis of compounds of the formula (I), using the latter for preparing agents modeling function of the nuclear hormone receptors. Compounds of the formula (I) can be used in treatment of prostate cancer.

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

8 cl, 11 tbl, 463 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to disinfectants. The composition is applied for disinfection and antiseptic preparation, including human and animal skin. The liposome biocide composition contains quaternary ammonium compound that is didecyldimethylammonium halogenide as urea clathrate, and lipid.

EFFECT: invention ensures high biocide activity and does not irritate the skin.

12 cl, 2 tbl, 4 ex

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