New compounds and their use as positive modulators of ampa receptors


C07D285/32 - with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 3

 

The present invention relates to new compounds of General formula I, where the bond indicated by a dashed line can be single bond, a double bond or is absent; and if this relationship is absent, the nitrogen substituted with hydrogen and R2; X represents SO2or C=O, or CH2; Y represents-CH(R4)-, -N(R4)- or-N(R4)-CH2- ;; And R2- R8defined in the application materials. These compounds are useful as positive modulators of AMPA receptors, which allow them to be used in therapy. Also described pharmaceutical composition on the basis of the claimed compounds. 2 C. and 24 C.p. f-crystals, 17 tab., table 2.

Description text in facsimile form (see graphic part) T T

Claims

1. The connection represented by the General formula (I)where X represents C=O or CH2Y - N(R4or O; R2is hydrogen; R3- cycloalkyl or alkyl, or R3- aryl; R4is hydrogen; R5is hydrogen;
R6is hydrogen;
R7is hydrogen; or
R7- -(alkyl)m-SO2-NR17R18where is the to which they are attached, form a heterocyclic 3-8-membered ring structure;
R8is hydrogen;
or a compound represented by the General formula (I),
where X - SO2;
Y - N(R4);
R2is hydrogen;
R3is hydrogen, cycloalkyl, alkyl, halogenated or alkoxy, or R3- carbocyclic 7-12-membered ring, or R3- benzyl, or R3together with R4and together with atoms to which they are attached, form a 4-7-membered ring;
R4hydrogen, or alkyl, or R4together with R3and together with atoms to which they are attached, form a 4-7-membered ring;
R5is hydrogen, halogen, alkyl, aryl or-SO2-NR11R12where R11and R12independently represent hydrogen;
R6is hydrogen, halogen, alkyl, alkoxy or cycloalkyl or R6- aryl, possibly substituted alkoxy, or R6represents NONE;
R7- halogen, alkyl, cyano, hydroxyalkyl or cycloalkyl, or
R7represents-NR17R18, -NHSO2-R17, -(alkyl)mSO-R17, -(alkyl)m-SO2-R17, -(alkyl)m-SO2OR17, -(alkyl)mNR17, -(alkyl)mNR17R18, -(alkyl)17and R18independently is hydrogen, alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or R7represents -(alkyl)m-SO2-NR17R18where m = 0 and R17and R18independently from each other - alkyl, cycloalkyl or aryl, or17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or
R7is a NO, possibly substituted by alkyl or aryl, or R7- aryl, possibly substituted one or more times with substituents selected from the group consisting of hydroxy, alkoxy, halogen, halogenoalkane, N-alkyl, nitro and-SO2-NR17R18where R17and R18independently is alkyl or cycloalkyl; or
R7together with R6or together with R8forms a 5-7-membered ring having St - aryl, possibly substituted alkoxy, or R8- NO,
provided, however, that if X is - SO2, a Y - NR4and if one of R5, R6, R7or R8is halogen, or alkyl, or alkoxy, one or more of the other R5, R6, R7or R8is not/are not also halogen or alkyl, and one or more of the other R5, R6, R7or R8is not/are not hydrogen.

2. Connection on p. 1, representing a derivative of 1,2,4-benzotiadiazina General formula (II)

where R3is hydrogen, cycloalkyl, alkyl, halogenated, alkoxy, carbocyclic 7-10-membered ring or benzyl, or R3together with R4and together with atoms to which they are attached, form a 5-6-membered ring;
R4is hydrogen or alkyl, or
R4together with R3and together with atoms to which they are attached, form a 5-6-membered ring;
R5is hydrogen, halogen, alkyl, phenyl, or-SO2-NR11R12where R11and R12independently is hydrogen;
R6is hydrogen, Br, F, I, cycloalkyl, alkyl or alkoxy, or R6is phenyl, which is possibly substituted alkoxy, or R6- NO;
R7Br, F, I18, -CR'=NOR", -CO-R17or-CO2-R17where R' and R" independently is hydrogen, alkyl or cycloalkyl and R17and R18independently is hydrogen, alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or
R7- -(alkyl)m-SO2-NR17R18where m = 0 and R17and R18independently from each other - alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or
R7- NO, possibly substituted by alkyl or phenyl;or
R7is phenyl, which is possibly substituted one or more times with substituents selected from the group consisting of hydroxy, alkoxy, halogen, halogenoalkane, -NHCO-alkyl, nitro and-SO2-NR17R18where R17and R18independently is alkyl or cycloalkyl; or
R7together with R8forms a 5-7-what does hydroxyalkyl, or R8- phenyl, possibly substituted alkoxy, or R8is a NO.

3. The compound of formula (I) under item 1, where R2- hydrogen.

4. The compound according to any one of paragraphs.1-3, where R3is hydrogen, cycloalkyl, alkyl, halogenated, alkoxy, carbocyclic 7-10-membered ring or benzyl, or R3together with R4forms a 5-6-membered ring.

5. The compound according to any one of paragraphs.1-4, where R4is hydrogen or alkyl, or R4together with R3and together with atoms to which they are attached, form a 5-6-membered ring.

6. The compound according to any one of paragraphs.1-5, where R5is hydrogen, halogen, alkyl, phenyl, or-SO2-NR11R12where R11and R12independently - hydrogen.

7. The compound according to any one of paragraphs.1-6, where R6is hydrogen, halogen, cycloalkyl, alkyl or alkoxy, or R6- aryl, which may substituted alkoxy, or R6- NO.

8. The compound according to any one of paragraphs.1-7, where R7- halogen, alkyl, cyano, hydroxyalkyl, cycloalkyl, -NHSO2-R17, -SO2-R17, -NHCOR17, -CONR17R18, -CR'= NOR", -CO-R17or-CO2-R17where R' and R" independently is hydrogen, alkyl or cycloalkyl and R17and R18independently is hydrogen, alkyl, cycloalkyl or aryl; or R17and R2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or R7represents -(alkyl)m-SO2-NR17R18where m = 0 and R17and R18independently - alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or R7- NO, which may substituted by alkyl or phenyl, or R7- phenyl, possibly substituted one or more times with substituents selected from the group consisting of hydroxy, alkoxy, halogen, halogenoalkane, -NHCO-alkyl, nitro and-SO2-NR17R18where R17and R18independently is hydrogen, alkyl or cycloalkyl; or R7together with R8form a 5-7-membered ring having the structure-O-(CH2)n-O-, where n = 1, 2, or 3.

9. The compound according to any one of paragraphs.1-8, where R8is hydrogen, alkyl, alkoxy or hydroxyalkyl, or R8is phenyl, which is possibly substituted alkoxy, or R8- NO.

10. The compound according to any one of paragraphs.1-9, where x IS the SO2Y is NH, R27- -(alkyl)mSO-R17, -(alkyl)m-SO2-R17, -(alkyl)mNR17R18, -(alkyl)m-CR'=NR", -(alkyl)m-CO-R17or -(alkyl)mCO2-R17where m = 0, R' and R" independently is hydrogen, alkyl or cycloalkyl, R17and R18independently is hydrogen, alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or R7- -(alkyl)m-SO2-NR17R18where m = 0, R17and R18independently - alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or R7"NO; or R7together with R8form a 5-7-membered ring having the structure-O-(CH2)n-O-, where n = 1, 2, or 3; R8- alkyl, or R8- NO.

11. The compound according to any one of paragraphs.1-10, where R3- modoran, the adamantane or benzyl, or R3together with R4and together with atoms to which they are attached, form a 5-membered ring.

12. The compound according to any one of paragraphs.1-11, where R4is hydrogen, methyl or ethyl, or R4together with R3and together with atoms to which they are attached, form a 5-membered ring.

13. The compound according to any one of paragraphs.1-12, where R5is hydrogen, chlorine, bromine, methyl or phenyl.

14. The compound of formula I according to any one of paragraphs.1-13, where R6is hydrogen, 2-methoxyphenyl, 2-pyridyl, 3-pyridyl, methyl, methoxy, chlorine or bromine.

15. The compound of formula I according to any one of paragraphs.1-14, where R7- chlorine, bromine, methyl, 1-hydroxyethyl, acetyl, -(CH3)CH=N-OH, -CONH2, -CO2-ethyl, cyano, phenyl, 2-nitrophenyl, 2-methoxyphenyl, 4-trifluoromethyl-2-methoxyphenyl, 2,4-acid, 2-N, N-dimethylsulphamoyl, 2-chlorophenyl, 2-forfinal, 3-hydroxyphenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-furyl, 3-furyl, 2-thienyl, 2-(N-methyl)-imidazolyl, 5-triazolyl, 4-phenyl-triazole-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, CH3N-, CH3SO2NH-, -SO2HE phenyl-SO2-, N,N-dimethylsulphamoyl, N,N-diethylcarbamoyl, N-phenyl-N-methyl-sulfamoyl or-SO2-heterocyclic ring, where the heterocyclic ring selected from the group vkluchaushsih and morpholine.

16. The compound of formula I according to any one of paragraphs.1-15, where R8is hydrogen, methyl, hydroxymethyl, 2-methoxyphenyl, 3-methoxyphenyl, 2-pyridyl or methoxy.

17. The compound of formula II under item 2, where R3- cyclohexyl, cyclopentyl, norbornene, norbornane, adamantane or ethoxy, R4is hydrogen or CH3, R5is hydrogen, CH3, phenyl, sulfamoyl, chlorine or bromine, R6is hydrogen, CH3, 2-methoxyphenyl, methoxy, bromine, 2-pyridyl or 3-pyridyl, R7- chlorine, bromine, methyl, 1-hydroxyethyl, acetyl, -(CH3)CH=N-OH, -CONH2, -CO2-ethyl, cyano, phenyl, 2-nitrophenyl, 2-methoxyphenyl, 4-trifluoromethyl-2-methoxyphenyl, 2,4-acid, 2-N, N-dimethylsulphamoyl, 2-chlorophenyl, 2-forfinal, 3-hydroxyphenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-furyl, 3-furyl, 2-thienyl, 2-(N-methyl)-imidazolyl, 5-triazolyl, 4-phenyl-triazole-6-yl, 5-methyl-1,2,4-oxadiazol-3-yl, -CH3N-, -CH3SO2NH-, -SO2OH, phenyl-SO2-, N,N-dimethylsulphamoyl, N,N-diethylcarbamoyl, N-phenyl-N-methyl-sulfamoyl or-SO2-heterocyclic ring, where the heterocyclic ring selected from the group comprising piperidine, pyrrolidine, 1,2,5,6-tetrahydropyridine, tetrahydroquinoline, N-methylpiperazine, N-sulfanilyl-piperazine and morpholine, R8where X is C=O, Y is NH or O, R2is hydrogen, R3is hydrogen, CH3, CF3, cyclohexyl, norbornene, phenyl or ethyl, R7is hydrogen, N, N-dimethylsulphamoyl, N-cyclohexylsulfamic, tetrahydropyran-1-yl-carboxylic acid morpholine-4-yl-sulfuric acid, sulfamoyl, bromine, R5is hydrogen or bromine and R4, R6and R8all hydrogen.

19. The compound of formula I under item 1, where X - CH2Y is NH, R3- cyclohexyl or norbornene, R5is hydrogen or bromine, R7- bromine or sulfamoyl, R2, R4, R6and R8all hydrogen.

20. The compound of formula I under item 1, where x IS the SO2Y is NH, R3- 3-methylbut-2-yl, phenyl or cyclohexyl and R7- 1-piperidinyl-sulphuric acid.

21. The compound of formula I under item 1, which is a
2-cyclohexyl-4-oxo-1,2,3,4-tetrahydroquinazolin,
2-phenyl-4-oxo-1,2,3,4-tetrahydroquinazolin,
2-methyl-3,4-dihydro-1,3-benzoxazin-4-one,
2-phenyl-3,4-dihydro-1,3-benzoxazin-4-one,
2-ethyl-2-methyl-3,4-dihydro-1,3-benzoxazin-4-one,
2-methyl-4-oxo-3,4-dihydro-6-hinzelin-N,N-dimethylsulfone,
2-trifluoromethyl-4-oxo-3,4-dihydro-6-hintline the sulfonamide,
2-trifluoromethyl-4-oxo-3,4-dihydro-6-hintline N,N-dimethylsulfone,
2-trifluoromethyl-4-oxo-3,4-dihydro-6-hinzelin-1', 2', 3', 6'-terraformer-4-oxo-3,4-dihydro-6-hintline morpholinosydnonimine,
2-cyclohexyl-4-oxo-3,4-dihydro-6-hinzelin-N,N-dimethylsulfone,
2-trifluoromethyl-4-oxo-3,4-dihydro-6-chinesesynchronous acid,
2 cyclohexylethylamine-5-N,N-dimethylaminobenzylidene or
2 ethylamino-7-(1',2',3',6'-tetrahydropyridine)sulfonylmethane or their pharmaceutically acceptable salt.

22. Derived 1,2,4-benzotiadiazina under item 2, which is a
3-bicyclo[2.2.1] hept-5'-EN-2'-yl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
1,2,3,5,10,10 and hexahydrobenzo[e] pyrrolo[1,2-b] -1,2,4-thiadiazine-5,5-dioxide,
3-cyclohexyl-6-(2-methoxyphenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-(2-pyridyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-(3-pyridyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(1-hydroxyethyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-acetyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(1-hydroxyimino)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-carbarnoyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-etoxycarbonyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-cyano-1,2,3,4-tetrahydro XID,
3-cyclohexyl-7-(2'-acetamidophenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-nitrophenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-methoxyphenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-methoxy-4'-triptoreline)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2', 4'-acid)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-(N, N-dimethylsulphamoyl)phenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-chlorophenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-forfinal)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(3'-hydroxyphenyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-pyridyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(3'-pyridyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-pyrimidinyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-furyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(3'-furyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(2'-thienyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-diox the 2', 3'-triazole-4'-yl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(5'-phenyl-1', 2', 3'-triazole-4'-yl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(5'-methyl-1', 2', 4'-oxidiazol-3-yl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-acetamido-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-methylsulfonylamino-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-phenylsulfanyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
2-cyclohexyl-1,2,3,4-tetrahydro-6-ChineseSimplified,
3-methyl-7-dimethylsulphamoyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
2-cyclohexyl-1,2,3,4-tetrahydro-6-hintline N,N-dimethylsulfone,
3-cyclohexyl-7-dimethylaminomethyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(N, N-diethylamino)sulfonyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-pyrrolidinecarbonyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-methyl-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclopropyl-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-isopropyl-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclopentyl-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
7-(1',2',3',6'-tetrahydropyridine)sulfonyl-1,2,3,5-tetrahydrobenzo[e] pyrrolo[2,1-C]-1,2,4-thiadiazine-5,5-dioxide,
3-bicyclo[2.2.1] hept-5'-EN-2'-yl-5,7-dimethyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7-(N, N-diethylcarbamoyl)-5-methyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-bicyclo[2.2.1] hept-5'-EN-2'-yl-5,7-diphenyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-methyl-7-(2'-pyridyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-methyl-7-(4'-triazolyl)-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclopentyl-6-methyl-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-methyl-7-morpholinomethyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-(2-methoxyphenyl)-7-methyl-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6-methoxy-7-piperidinemethanol-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-7,8-Ethylenedioxy-1,2,3,4-tetrahydro-1,2,4-benzothiadiazine-1,1-dioxide,
3-cyclohexyl-6,7-Ethylenedioxy-1,2,3,4-tetrahydro-1,1-dioxide or its pharmaceutically acceptable salt.

23. The compound of General formula (III)

where Y Is N(R4);
R4is hydrogen or alkyl;
R3- carbocyclic 7-12-membered ring;
R6- halogenoalkane;
R7- halogen, alkyl, cyano, hydroxyalkyl or cycloalkyl; or
R7- -(alkyl)m-SO2-R17, -(alkyl)m-SO2OR17, -(alkyl)mNR17, -(alkyl)mNR17R18, -(alkyl)m-CR'=NR", -(alkyl)mWITH-R17or -(alkyl)mCO2-R17where m = 0, R' and R" independently is hydrogen, alkyl or cycloalkyl and R17and R18independently is hydrogen, alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted by alkyl or-SO2-alkyl, and perhaps it is a heterocyclic ring condensed with aryl; or
R7- -(alkyl)m-SO2-NR17R18where m = 0, R17and R18independently from each other - alkyl, cycloalkyl or aryl, or R17and R18together with the nitrogen atom to which they are attached, form a heterocyclic 3-8-membered ring structure which may be substituted, alkalo is T, possibly substituted by alkyl; or
R7- aryl, possibly substituted one or more times with substituents selected from the group consisting of hydroxy, alkoxy, halogen, halogenoalkane, N-alkyl, nitro and-SO2-NR17R18where R17and R18independently is alkyl or cycloalkyl; or
R7together with R6forms a 5-7-membered ring having the structure-O-(CH2)n-O-, where n = 1, 2, or 3.

24. Pharmaceutical composition having properties modulators of AMPA receptors containing an effective amount of a chemical compound according to any one of paragraphs.1-23 or its pharmaceutically acceptable salt and pharmaceutically acceptable excipient, carrier or diluent.

25. Connection under item 1 for use for the preparation of drugs for the treatment of a disorder or disease of a living animal body, including a human, with a disorder or disease is responsive to modulation of AMPA-receptor complex of the Central nervous system.

26. Connection on p. 25, where the disorder or disease selected from disorders of memory and impaired ability to learn, psychotic disorders, sexual dysfunction, deterioration of mental abilities, schizophrenia, gearchecks dementia or from disorders or diseases, resulting from trauma, stroke, epilepsy, Alzheimer's disease, exposure to neurotoxic agents, aging, neurodegenerative disorders, alcohol intoxication, substance abuse, surgery using the heart-lung machine or cerebral ischemia.

 

Same patents:

The invention relates to new derivatives of benzothiazole General formula (I) or its salt, where p denotes 1; X1and X2together form =O; R1denotes hydrogen, halogen, alkyl, alkoxy; R2denotes hydrogen; R3denotes a-Z4-R6, -Z13-NR7R8; Z4denotes a-Z11-C(O)-Z12-, -Z11-C(O)-O-Z12-; Z11and Z12represent a simple bond or alkylene; Z13denotes a-Z11-C(O)-Z12-; R4denotes hydrogen; R5denotes phenyl, substituted groups Z1, Z2selected from alkyl, halogen, nitro, -HE, hydroxyalkyl, -C(O)Z6, -C(O)OZ6-Z4-NZ7Z8where Z4represents a simple bond; biphenyl, substituted alkyl; naphthalenyl, which optionally can be substituted-HE; chinoline, substituted alkyl; heterocyclics; Z6denotes alkyl which may be optionally substituted by a group-Z4-NZ7Z8, morpholinium; Z7, Z8each independently represents alkyl; R6denotes alkyl optionally substituted by cyano, methoxy, phenyl, -Z4-NZ7Z8and so on; R7denotes hydrogen, alkyl; R8denotes alkyl, the long is Z4-NZ7Z8; and t

The invention relates to new derivatives of aminothiazole formula I and their pharmaceutically acceptable salts, where R1and R2independently of one another denote hydrogen, fluorine or lower alkyl; R3denotes heteroaryl selected from oxazolyl, which is substituted by one or more substituents selected from lower alkyl, halogen, carbamoyl, allyloxycarbonyl, alkylcarboxylic; or benzoxazole; R4denotes hydrogen;-alkyl which can be optionally substituted with halogen, alkoxy, hydroxy, allyloxycarbonyl, alkylcarboxylic, amino, carbamoyl; CO-cycloalkyl; CO-aryl, where aryl represents phenyl which may be optionally substituted with halogen, lower alkyl, alkoxy, amino, cyano or naphthyl, and so on; or COO-alkyl; COO-cycloalkyl; soo-phenyl; COO-alkyl-phenyl; SO2-alkyl; SO2-phenyl, C(NCN)NH-phenyl, where phenyl may be optionally substituted with halogen; R5denotes hydrogen; m is an integer from 0 to 2; n is 0

The invention relates to amino acid derivatives of the formula I

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or its non-toxic salt or its hydrate, the pharmaceutical composition having inhibitory effect on calcium channel iv-type; the inhibitor calcium channel N-type; a pharmaceutical composition for prevention and/or treatment of cerebral infarction and pharmaceutical compositions for the treatment of pain

The invention relates to a derivative of sulfoaluminate and sulphoniumhydroxide acid of formula I, its pharmaceutically acceptable salts, where W is-HE-or-NHOH; X denotes (a) a heterocyclic radical selected from the group comprising imidazolines, dihydrobenzofuranyl and so on, b) -NR1SO2R2where R1denotes a hydrogen atom, R2denotes an unsubstituted phenylalkyl and so on; Y represents carbon or sulfur, with the proviso that when Y represents carbon, n is equal to 2; Z represents phenyl, optionally substituted with halogen, unsubstituted alkoxy, phenyloxy, optionally substituted with halogen, phenylacetonitrile, 4-methylpiperazine, 4-phenylpiperidine, pyridyloxy, -NR'1COR'2, -SO2R'2where R'1denotes a hydrogen atom, R'2denotes phenyl, optionally substituted by hydroxy or phenyl, pyridinyl, substituted-CF3; m denotes an integer from 1 to 4, n represents an integer of 1 or 2

The invention relates to new cyclic diamine compounds of the formula I, where

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represents an optionally substituted divalent residue of benzene, where the substituents are selected from unsubstituted lower alkyl groups, unsubstituted lower alkoxygroup, unsubstituted lower acyl group, a lower allylthiourea, lower alkylsulfonyl group, halogen atom, etc. or unsubstituted pyridine; Ar represents a phenyl group which may be substituted by one to four groups selected from unsubstituted lower alkyl group, the unsubstituted alkoxygroup, low allylthiourea, lower alkylsulfonyl group, and so on, optional substituted amino group, alkylenedioxy; X is-NH-, oxygen atom or sulfur atom; Y is a sulfur atom, sulfoxide or sulfon; Z represents a single bond or-NR2-; R2- the atom of hydrogen or unsubstituted lower alkyl group; l = 2 or 3; m = 2 or 3; n = 1, 2, or 3, or their salts, or their solvate

The invention relates to new derivatives isothiazolinones acid of the formula I, where R stands for a group-OR1or-SR2in which R1means alkyl with 1-6 carbon atoms, a substituted once residues selected from the group comprising halogenoalkanes with 1-6 carbon atoms and 1 to 5 halogen atoms, dialkylamino with 1-6 carbon atoms in each alkyl part, phenylalkyl with 1-4 carbon atoms in the CNS parts and pyrrolidinyloxyl with 1-4 carbon atoms in the CNS part, and twice by hydroxyl, or so, m and n is 2, R3means phenyl, R4means alkyl with 1-4 carbon atoms, R2means alkyl with 1-6 carbon atoms, or R2means phenylalkyl with 1-2 carbon atoms in the alkyl part, with the phenyl portion may be substituted with halogen

The invention relates to a new derivative of solidilin formula (I) where one of X, Y and Z represents C=O or C=S, and one of the remaining X, Y and Z denotes a group With=, and the other group C=S; R1, R2and R3are Deputy or X, Y and Z, or nitrogen atom and may be the same or different and denote hydrogen, halogen, hydroxy, nitro, etc., the group -(CH2)n-O - and may be joined through the nitrogen atom, or X, Y, Z, n is 1-4, Ar denotes a phenylene or naftilan, R4denotes hydrogen or forms a bond with group a, And denotes nitrogen or CR5, R5denotes hydrogen, halogen or forms a bond with R4In means O or S, when a is CR5and means that, when a is N, its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt and solvate

The invention relates to the derivatives of propanolamine formula (I) and their pharmaceutically acceptable salts, where R1and R2means phenyl, naphthyl, pyridyl, thienyl, pyrimidyl, thiazolyl, hinely, piperazinil, oxazolyl, which may be substituted with halogen, HE, NO2, NH2, COOH, etc., R3-R8mean hydrogen, hydroxyl, (C1-C8-alkoxy, NH2-THE OTHER9, -N(R9R10, R9-R10mean hydrogen or (C1-C8)alkyl, X is CH or N, Y represents CH or N, provided that the residues R1, R2X and Y are not simultaneously mean R1- phenyl, R2is phenyl, X is CH, Y is CH

The invention relates to the derivatives of pyrrolidine formula I

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where R1- H, C1-C6alkyl; phenyl, possibly substituted; biphenyl, possibly substituted; 1H, 5H - pyrido [3,2,1-ij] chinolin; phenyl WITH1-C6alkyl, optionally substituted; biphenyl WITH1-C6alkyl, optionally substituted; biphenylcarboxylic; terphenyl; naphthyl, optionally substituted; Z denotes-S-, -O-, -och2-, -N(R16), where R16- H, C1-C6alkyl, C3-C8cycloalkyl1-C6alkyl, panels1-C6alkyl, a chemical bond; X1means-CO-, -(CH2)r-CO-N(R17), where R17means H, C1-C6alkyl (where r = 0 or 1), -CH2NHSO2-, -(CH2)s-N (R18)-CO- (where R18- N, s=1-3), - CH2NHCОСН2O-, -CH2N (R19Of PINES = CH- (where R19- H, -CH2OCH2-, -CH2-N (R20)-CH2- (where R20- H, C1-C6alkyl, C1-C6alkylsulphonyl, phenylcarbinol)1-C5alkylen,2-C4albaniles, a chemical bond; X2- phenylene, optionally substituted hydroxy, theoffender, purandar, piperidinyl,< / BR>
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R2and R3each - H; and R4- phenyl, possibly substituted with halogen; R5- phenyl, possibly substituted; a cycle of G is phenyl,3-C7cycloalkyl, pyridyl, thienyl; loop J is phenyl; L is phenyl; p=0-2;----- means the presence or absence of chemical bonding;displays a CIS - or TRANS-configuration D relative to E; provided that X1means-CH2NHCО-, X2means 1,4-phenylene and X3means a chemical bond or a C1-C5alkylen, when the carbon atom bound CD and adjacent carbon atom in the cycle are connected by a simple relation and V1does not mean a chemical bond, when X1means-CH2O-; and pharmaceutically acceptable salt or hydrate of the compound

The invention relates to a derivative of 1,2,4-thiadiazole, substituted in the 5-position of General formula I, in which X Is N; R1- C1-6alkyl; R2is hydrogen, R3, R4and R5each independently selected from hydrogen; trifloromethyl;is Ar2, Ar2CH2or Het2; AG2is phenyl; Het2is a monocyclic heterocycle selected from thiadiazolyl, pyridinyl, pyrimidinyl or pyrazinyl, their N-oxide forms, the pharmaceutically acceptable acid additive salts and stereochemical isomeric forms

The invention relates to new heterocyclic compounds of the formula (I), where R1represents a group of formula (II), R is 2,4-dioxothiazolidine-5-ylmethylene group and others, And represents C1-6alkylenes group, A represents an oxygen atom, R4represents a substituted phenyl or pyridyl which may have a Deputy, R6represents a hydrogen atom or a C1-6alkyl group, D represents an oxygen atom or sulfur, E is a CH group or a nitrogen atom, or their pharmacologically acceptable salts

The invention relates to new 1,4-benzothiazepine-1,1-dioxides of the formula (I), where R1is non-branched C1-6alkyl group, R2is non-branched C1-6alkyl group, R3is hydrogen, R4represents phenyl, R5R6and R8selected from hydrogen, R7represents a group of formula (Ia) and (IB), where the hydroxy-group may be substituted by acetyl, R16represents-COOH, -CH2-OH, -CH2-O-acetyl-Sooma, R9and R10the same or different and each represents hydrogen or C1-6alkyl group, X represents-O-, or its salt, solvate and physiologically acceptable derivative

The invention relates to novel potassium salts derived biphenylmethane - mono - or dicale 2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4-thiadiazoline-2-ilidene] aminocarbonyl] -1-cyclopentanecarboxylate having anti-hypertensive activity

The invention relates to a derivative of a simple ester, application and intermediate compounds used for their production

The invention relates to new preparations of thiazolidinediones of the formula I, where A denotes a carbocyclic ring with 5 or 6 carbon atoms or a heterocyclic aromatic 5-or 6-membered ring containing an S atom or N; B is-CH=CH-; W represents O; X represents O; Y represents N; R represents pyridyl, thienyl or phenyl, in case you need one - or disubstituted C1-C3-alkyl, CF3, Cl or bromine; R1represents C1-C6-alkyl;n represents 2, and their tautomers, enantiomers, diastereomers or physiologically acceptable salts and medicinal product on the basis of their

The invention relates to heterocyclic compounds having excellent pharmacological properties, and to intermediate compounds used for the synthesis of these compounds

The invention relates to a neuroprotective (anti-ischemic and excited by blocking amino acid receptor) analogues 5-(1-hydroxy-2-piperidinophenyl)-2-(1H, 3H)-indole-defined formula (I), (II) and (III) below; their pharmaceutically acceptable salts; method of using these compounds in the treatment of stroke, traumatic brain injury or degenerative diseases of the CNS (Central nervous system), such as disease Alzheimer, senile dementia Alzheimers.com type, Huntington's disease and Parkinson's disease; and some of their intermediates
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