Indazoles, bentothiazoles, benzoisothiazoles, benzisoxazoles and synthesis and use thereof

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I in which A denotes X denotes O; R denotes H; R1 denotes OH, CN, a nitro group, NH2, NR2CSR8, NR2CONR2R9, NR2C SNR2R9, NR2SO2R10, NR2CONR6R7, NR2CSNR6R7, NR2R9, SO2R10, SOR10, alkyl containing 1-4 carbon atoms, fluorinated alkyl containing 1-4 carbon atoms, alkenyl containing 2-6 carbon atoms, alkynyl containing 2-6 carbon atoms, where each alkyl, fluorinated alkyl, alkenyl or alkynyl group in each case is unsubstituted or substituted with Ar or He, cycloalkenyl containing 5-8 carbon atoms, alkoxy group containing 1-4 carbon atoms, cycloalkoxy group containing 3-7 carbon atoms, cycloalkylalkoxy group containing 4-7 carbon atoms, fluorinated alkoxy group containing 1-4 carbon atoms, fluorinated hydroxyalkyl containing 1-4 carbon atoms, hydroxyalkoxy group containing 2-4 carbon atoms, an ordinary hydroxyalkoxy group containing 2-4 carbon atoms, monoalkylamino group containing 1-4 carbon atoms, dialkylamine group, where each alkyl group independently contains 1-4 carbon atoms, alkoxycarbonyl containing 2-6 carbon atoms, Het or OAr; R2 denotes H, alkyl containing 1-4 carbon atom, cycloalkyl containing 3-7 carbon atoms, and cycloalkyl alkyl containing 4-7 carbon atoms; R6 and R7 independently denote H, alkyl containing 1-4 carbon atoms, cycloalkyl containing 3-7 carbon atoms, or cycloalkylalkyl containing 4-7 carbon atoms, or R6 and R7 together denote an alkylene group containing 4-6 carbon atoms, which forms a ring with an N atom; R8 denotes alkyl containing 1-4 carbon atoms, fluorinated alkyl containing 1-4 carbon atoms, alkenyl containing 3-6 carbon atoms, alkynyl containing 3-6 carbon atoms, where each alkyl, fluorinated alkyl, alkenyl or alkynyl group is unsubstituted or substituted with Ar, cycloalkyl containing 3-7 carbon atoms, or Het; R9 denotes Ar or Het; R10 denotes alkyl containing 1-4 carbon atoms which is unsubstituted or substituted with Ar, or NR6R7; Ar denotes an aryl group containing 6-10 carbon atoms, which is unsubstituted or substituted once or several times with an alkyl containing 1-8 carbon atoms, alkoxy group containing 1-8 carbon atoms, halogen, cyano group or combinations thereof; and Het denotes dihydropyranyl, tetrahydropyranyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, isoxazolinyl, thiazolyl, oxazolyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, isoquinolinyl or naphthyridinyl, which is unsubstituted or substituted once or several times with halogen, aryl containing 6-10 carbon atoms, which is optionally substituted with alkyl containing 1-8 carbon atoms, alkoxy group containing 1-8 carbon atoms, oxo group, -CXR11 or combinations thereof, or R11 denotes alkyl containing 1-4 carbon atoms which is unsubstituted or substituted with Ar or Het; or pharmaceutically acceptable salts thereof, where formula IA is attached to the rest of the bonding molecule in the 3, 4 or 7 positions. The invention also relates to a pharmaceutical composition and to use of compounds in any of claims 1-37.

EFFECT: obtaining novel biologically active compounds, having nicotinic acetylcholine receptor subtype α7 ligand activity.

59 cl, 316 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

(I)
where And denotes

X denotes O;
R' denotes H;
R1seat the o HE, CN, a nitrogroup, NH2, NR2CSR8, NR2CONR2R9, NR2CSNR2R9, NR2SO2R10, NR2CONR6R7, NR2CSNR6R7, NR2R9, SO2R10, SOR10, alkyl containing 1-4 carbon atoms, fluorinated alkyl containing 1-4 carbon atoms, alkenyl containing 2-6 carbon atoms, quinil containing 2-6 carbon atoms, where each alkyl, fluorinated alkyl, Alchemilla or Alchemilla group in each case is unsubstituted or substituted with AG or Het, cycloalkenyl containing 5-8 carbon atoms, alkoxygroup containing 1-4 carbon atoms, cycloalkanes containing 3-7 carbon atoms, cycloalkylcarbonyl containing 4-7 carbon atoms, a fluorinated alkoxygroup containing 1-4 carbon atoms, fluorinated hydroxyalkyl containing 1-4 carbon atoms, hydroxyalkoxy, containing 2-4 carbon atoms, a fluorinated hydroxyalkoxy containing 2-4 carbon atoms, monoalkylamines containing 1-4 carbon atoms, dialkylamino, where each alkyl group independently contains 1 to 4 carbon atom, alkoxycarbonyl containing 2-6 carbon atoms, Het or OAS;
R2denotes H, alkyl containing 1-4 carbon atoms, cycloalkyl containing 3-7 carbon atoms, or cycloalkenyl containing 4-7 carbon atoms;
R6and R7all independently denote H, alkyl containing 1-4 carbon atoms, cycloalkyl containing 3-7 carbon atoms, or cycloalkenyl containing 4-7 carbon atoms, or R6and R7together denote alkylenes group containing 4-6 carbon atoms which forms a ring with the N atom;
R8denotes alkyl containing 1-4 carbon atoms, fluorinated alkyl containing 1-4 carbon atoms, alkenyl containing 3-6 carbon atoms, quinil containing 3-6 carbon atoms, where each alkyl, fluorinated alkyl, Alchemilla or Alchemilla group is unsubstituted or substituted with AG, cycloalkyl containing 3-7 carbon atoms, or Het;
R9denotes AG or Het;
R10denotes alkyl containing 1-4 carbon atoms, which is unsubstituted or substituted with AG, or NR6R7;
AG denotes aryl group containing 6-10 carbon atoms, which is unsubstituted or one or more times substituted by alkyl containing 1 to 8 atoms, alkoxygroup containing 1 to 8 C atoms, halogen, cyano or combinations thereof; and
Het denotes dihydropyran, tetrahydropyranyl, tetrahydrofuranyl, tetrahydrothieno, pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, isoxazolyl, thiazolyl, oxazolyl, pyrrolyl, pyrazolyl, and imazalil, pyridyl, pyrimidinyl, indolyl, chinoline, ethenolysis or naphthyridine, which is unsubstituted or one or more substituted with halogen, aryl containing 6 to 10 carbon atoms, which optionally is substituted, alkyl containing 1 to 8 atoms, alkoxygroup containing 1-8 C atoms, exography, -CXR11or their combinations, or
R11denotes alkyl containing 1-4 carbon atoms, which is unsubstituted or substituted with AG or Het; or
its pharmaceutically acceptable salt, and
formula IA is attached to the rest of the molecule compounds 3, 4 or 7 position.

2. The compound according to claim 1, in which R1means quinil containing 2-6 carbon atoms, fluorinated hydroxyalkyl containing 1-4 carbon atoms, or AG-quinil.

3. The compound according to claim 1, in which the indicated compound described by formula I, R2denotes H or alkyl, and R1denotes CN, NO2, NH2, fluorinated alkyl, alkoxygroup, the fluorinated alkoxygroup, fluorinated hydroxyalkyl, quinil, cycloalkylcarbonyl, AG-quinil or Het.

4. The compound according to claim 3 in which R1denotes NH2, CF3The co3OC2H5, F3, 2,2,2-Cryptor-1-hydroxy-1-(trifluoromethyl)ethyl ethinyl, PROPYNYL, pentenyl, cyclopropylmethoxy, phenylethynyl, d is hydroporini, thiazolyl, oxazolyl, pyrrolidinyl, piperidinyl or morpholinyl.

5. The compound according to claim 1, in which the indicated compound described by formula I, and group a is attached to the remainder of the connection in position 3.

6. The compound according to claim 1, in which the indicated compound described by formula I, and group a is attached to the remainder of the connection in position 4.

7. The compound according to claim 1, in which the indicated compound described by formula I, and group a is attached to the remainder of the connection in position 7.

8. The compound according to claim 1, in which the alkyl in each case, means methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl.

9. The compound according to claim 1, in which alkoxygroup in each case means methoxy, ethoxy-, propoxy-, isopropoxy, isobutoxy - or second-butoxypropan.

10. The compound according to claim 1, in which cycloalkyl in each case means cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

11. The compound according to claim 1, in which AG in each case denotes phenyl, naphthyl or biphenyl, which is optionally substituted.

12. The compound according to claim 1, in which R1denotes NH2, CF3The co3OS2H5, F3dihydropyran, thiazolyl, oxazolyl, pyrrolidinyl, piperidinyl or morpholinyl.

13. The compound according to claim 1, where the specified connection is selected from a group including:
6-amino-N-[(3S)-1-asabis the CLO[2.2.2]Oct-3-yl]-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(cyclohex-1-EN-1-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(tetrahydro-2H-Piran-4-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(triptoreline)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-ethinyl-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-hydroxy-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-phenoxy-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-piperidine-1-yl-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-pyrrolidin-1-yl-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3R)1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-4-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(Penta-1-Jn-1-yl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(phenylethynyl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-and the]-6-(trifluoromethyl)-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-ethinyl-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-hydroxy-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-methoxy-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-morpholine-4-yl-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-piperidine-1-yl-1H-indazol-3-carboxamid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-pyrrolidin-1-yl-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(tetrahydro-2H-Piran-4-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(triptoreline)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-ethinyl-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-nitro-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-4-yl)-1H-indazol--carboxamide,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(morpholine-4-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(prop-1-Jn-1-yl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(trifluoromethyl)-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-[2,2,2-Cryptor-1-hydroxy-1-(trifluoromethyl)ethyl]-1H-indazol-3-carboxamid,
N-(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-ethinyl-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-methoxy-1H-indazol-3-carboxamid,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-nitro-1H-indazol-3-carboxamide, and their physiologically acceptable salts.

14. The compound according to claim 1, where the connection specified is presented in the form of cleaners containing hydrochloride, hydroforming or hydrotartrate salt.

15. The connection 14, where the specified connection is selected from a group including:
hydroformed 3-{[(3R)-1-azabicyclo[2.2.2]Oct-3-ylamino]carbonyl}-1H-indazol-6-carboxylic acid,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(cyclohex-1-EN-1-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(triptoreline)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-ethinyl-1H-indazol-3-carboxamid drochloride,
N-[(3R)-1-azabicyclo [2.2.2]Oct-3-yl]-5-ethinyl-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-hydroxy-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2,2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-phenoxy-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-piperidine-1-yl-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxyhemoglobin,
N-[(3R)-1-azabicyclo[2,2 .2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-4-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(Penta-1-Jn-1-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(phenylethynyl)-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-ethinyl-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-hydroxy-1H-indazol-3-carboxymethyloxime,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-methoxy-1H-indazol-3-carboxyhemoglobin,
N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-piperidine-1-yl-1H-indazol-3-carboxamidotryptamine the tat,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(triptoreline)-1H-indazol-3-carboxyhemoglobin,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(triptoreline)-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-ethinyl-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxyhemoglobin,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-4-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(prop-1-Jn-1-yl)-1H-indazol-3-carboxymethyloxime,
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxymethyloxime and
N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-ethinyl-1H-indazol-3-carboxymethyloxime.

16. The compound according to claim 1, where the specified connection is a N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

17. The compound according to claim 1, where the specified connection to depict the place of a N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-hydroxy-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

18. The compound according to claim 1, where the specified connection is a N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-hydroxy-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

19. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-methoxy-1H-indazol-3-carboxamid or its pharmaceutically acceptable salt.

20. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-methoxy-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-methoxy-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-methoxy-1H-indazol-3-carboxamid or its pharmaceutically acceptable salt.

21. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo [2.2.2]Oct-3-yl]-5-triptoreline-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-triptoreline-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-triptoreline-1H-indazol-3-carboxamid or its pharmaceutically acceptable salt.

22. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2,2 .2]Oct-3-yl]-6-triptoreline-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-triptoreline-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-the l]-6-triptoreline-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

23. The compound according to claim 1, where the specified connection is a N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyclopropylmethoxy-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

24. The compound according to claim 1, where the specified connection is a N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-pyrrolidin-1-yl-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

25. The compound according to claim 1, where the specified connection is a N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-pyrrolidin-1-yl-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

26. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-morpholine-1-yl-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-morpholine-1-yl-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2,2]Oct-3-yl]-6-morpholine-1-yl-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

27. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-5-(tetrahydro-2H-Piran-4-yl)-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(tetrahydro-2H-Piran-4-yl)-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(tetrahydro-2H-Piran-4-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

28. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-yl)-1H-indazol-3-carboxamid, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-4-yl)-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(3,6-dihydro-2H-Piran-4-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

29. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

30. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-thiazol-2-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

31. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

32. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-oxazo the-2-yl)-1H-indazol-3-carboxamid, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1,3-oxazol-2-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

33. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

34. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-cyano-1H-indazol-3-carboxamid or its pharmaceutically acceptable salt.

35. The compound according to claim 1, where the specified connection is a N-[1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxamide, N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxamide, N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-6-cyano-1H-indazol-3-carboxamid or its pharmaceutically acceptable salt.

36. The compound according to claim 1, where the specified connection is a N-[(3R)-1-azabicyclo[2.2.2]Oct-3-yl]-5-piperidine-1-yl-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

37. The compound according to claim 1, where the specified connection is a N-[(3S)-1-azabicyclo[2.2.2]Oct-3-yl]-5-tripto the methoxy-1H-indazol-3-carboxamide or its pharmaceutically acceptable salt.

38. Pharmaceutical composition having activity of ligands of nicotinic acetylcholine receptor α7 subtype, comprising the compound according to any one of claims 1 to 37 and a pharmaceutically acceptable carrier.

39. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the selective activation/stimulation of the α-7 nicotinic receptor, wherein such activation/stimulation has a therapeutic effect.

40. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of mental diseases, neurodegenerative diseases involving a dysfunction of the cholinergic system, and/or pathological conditions of memory and/or impairment of cognitive ability.

41. Use p in which the specified drug is intended for treatment of schizophrenia, anxiety, mania, depression, manic depression, Tourette's syndrome, Parkinson's disease, Huntington's disease, Alzheimer's disease, dementia, when developing the disease diffuse Taurus Levi, amyotrophic lateral sclerosis, memory impairment, memory loss, lack of cognitive abilities, attention deficit, and/or attention deficit disorder with hyperactivity.

42. The use of compounds according to any one of claims 1 to 37 for making the medication is the main treatment for dementia and/or other pathological condition, accompanied by memory loss.

43. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of memory impairment caused by age impaired cognitive abilities in mild Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, diseases of the Peak of the disease of Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral fading, multi-infarct dementia, HIV, and/or cardiovascular diseases.

44. The use of compounds according to any one of claims 1 to 37 for the preparation of a medicinal product for treating and/or preventing dementia in a patient suffering from Alzheimer's disease, by inhibiting the binding of an amyloid beta-peptide with nACh receptors.

45. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of alcohol withdrawal syndrome or protivoinfektsionnogo therapy.

46. The use of compounds according to any one of claims 1 to 37 for the preparation of medicines to ensure neurotoxity from damage associated with strokes and ischemia, caused by glutamate excitotoxicity impact.

47. The use of compounds according to any one of claims 1 to 37 for the preparation of a medicinal product for treatment of nicotine addiction, pain, de is increase, obesity and/or diabetes.

48. The use of compounds according to any one of claims 1 to 37 for the preparation of a medicinal product to promote Smoking cessation patient.

49. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of disorders of cognitive ability in the form of light (NPL), multi-infarct dementia (VaD), age-related deterioration of cognitive abilities (WUPS), amnesia associated with open heart surgery, cardiac, General anesthesia, attention deficit due to the impact of anaesthetics caused by sleep deprivation disorders cognitive abilities, chronic fatigue syndrome, narcolepsy associated with AIDS dementia associated with epilepsy disorders cognitive abilities of down syndrome associated with alcoholism dementia caused by drug addiction/substance abuse disorders memory traumatic dementia (syndrome boxer), or dementia in animals.

50. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of memory loss.

51. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of memory disorders.

52. The application of § 51, in which the specified memory impairment due to decreased activity of nicotine is cetylcholine receptor.

53. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for treatment or prevention of diseases or pathological conditions caused by disorders of the transfer function of nicotinic acetylcholine receptor, defective or malfunctioning nicotinic acetylcholine receptors, or due to the suppression of the transmission of nicotinic acetylcholine receptor.

54. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for treatment or prevention of diseases or pathological conditions caused by loss of cholinergic synapses.

55. The use of compounds according to any one of claims 1 to 37 for the preparation of a medicinal product to protect neurons from the neurotoxic effects caused by activation of α7nACh receptors.

56. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for treatment or prevention of neurodegenerative disorders by inhibiting the binding of peptides β with α7nACh receptors.

57. The use of compounds according to any one of claims 1 to 37 for the preparation of drugs for the treatment of inflammatory diseases.

58. The application of § 57, in which the specified inflammatory disease is a rheumatoid arthritis, diabetes or sepsis.

59. the label on any of PP-58, in which the specified patient is a man.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula IB , where radicals R1-R5 have values, given in invention formula. In range of claimed invention also described are pharmaceutical compositions, which include compounds of IB formula, and methods of application of such compounds and compositions for treatment of different malfunctions, mainly selected from immune response reactions.

EFFECT: compounds by claimed invention have inhibiting action with respect to proteinkinases and, in particular with respect to JAK-3, ROCK or Aurora kinases.

55 cl, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives of general formula , where R is an optional ortho- or meta-substitute selected from halogen and (C1-4)alkyloxy; R1 is halogen or CF3; R2 is H, (C1-4)alkyloxy or halogen; R3 is H or (CH2)n-NR5R6; R4 is H or (C1-6)alkyl, optionally substituted COOR7 or NR8R9; R5 and R6 independently denote H, (C3-8)cycloalkyl, quinuclidin-3-yl, (C2-6)alkenyl or (C1-6)alkyl, optionally substituted mono-substituted with CF3, (C3-8)cycloalkyl, (C6)aryl, a 5- or 6-member heteroaryl group, OH, (C1-6)alkyloxy, (C6-10)aryloxy, CONR11R12, NR13R14 or NR13SO2(C1-4)alkyl; or R5 and R6 together with a nitrogen atom to which they are bonded form a 4-8-member saturated heterocyclic ring which also contains 1 heteroatom selected from O, SO2 and NR15, where the ring is optionally mono-substituted or di-substituted with oxo, (C1-4)alkyl, (C3-8)cycloalkyl, NR16R17 or CONR18R19; R7 is H or (C1-4)alkyl; R8 and R9 independently denote H, (C1-4)alkyl (optionally substituted di(C1-4)alkylamino) or (C3-8)cycloalkyl; or R8 and R9 together with a nitrogen atom with which they are bonded form a 4-8-member saturated heterocyclic ring which also contains one heteroatom which is O; R11 and R12 independently denote H or (C1-4)alkyl; R13 and R14 independently denote H or (C1-4)alkyl; R15 is H, (C1-4)alkyl (optionally mono-substituted OH, (C1-4)alkyloxy or di(C1-4)alkylamino), phenyl, pyridyl or COR20; R16 and R17 denote (C1-4)alkyl; or R16 and R17 together with a nitrogen atom with which they are bonded from a 4-8-member saturated heterocyclic ring; R18 and R19 denote H; R20 is (C1-4)alkyl, (C3-8)cycloalkyl or furyl; and n equals 0 or 1; or its pharmaceutically acceptable salt. The invention also relates to use of formula I compounds to prepare a medicinal agent and to a pharmaceutical composition based on formula I compound.

EFFECT: novel derivatives have catepsin S and K inhibitory activity.

9 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: new compounds have formula (I) , where values of radicals R1 - R10 are as given in paragraph 1 of the formula of invention; n equals 2 or 3, --- denotes absence of substitution or a single bond; and denotes a single bond or a double bond, or to salts thereof. The invention also relates to a method of producing compounds of formula (Ic), to a NK2 receptor antagonist, to a pharmaceutical agent, to a method of antagonising the NK2 receptor, to a method of preventing or treating functional gastrointestinal diseases, as well as to use of compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds with antagonistic effect on the NK2 receptor.

31 cl, 331 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of photoactivation of a photocatalyst by irradiating a composition containing the said catalyst. The method of using a photolatent catalyst (a) in which a composition containing said catalyst is irradiated before subsequent treatment is characterised by that, the photolatent catalyst is: (a1) a compound selected from a group consisting of a photolatent acid, an aromatic iodonium salt or oxime-based photolatent acid; (a2) a photolatent base compound. Also described is a substrate on which a coating made from the composition is deposited in accordance with the above described method. Also described is a method of using photolatent catalyst (a), in which a composition containing said catalyst is irradiated before subsequent treatment, characterised by that subsequent treatment is preparation of foam material and the composition contains polyol and isocyanate components and photolatent base (a2) as photolatent catalyst.

EFFECT: provision for solidification of the system.

13 cl, 10 tbl, 16 ex

FIELD: pharmacology.

SUBSTANCE: present invention refers to compounds of formula (I) , to its N-oxides, salts, stereoisomer forms where n is equal 1, 2 or 3; R1 means cyano group; X means bivalent radical NR2 or O; R2 means hydrogen or C1-10alkyl, each Q1 independently stands for direct coupling, -CH2- or -CH2-CH2-; each R4 independently means hydrogen or C1-4alkyl; each R5a, R5b, R5c independently means hydrogen, C1-4alkyl or arylC1-4alkyl; each R5e, R5f independently means hydrogen, C1-4alkyl or arylC1-4alkyl, or R5e and R5f together can form bivalent alkandiyl radical of formula -CH2-CH2- or -CH2-CH2-CH2-; R11 means aryl, arylC1-4alkyl, C1-4alkylcarbonyl, arylcarbonyl, arylC1-4alkylcarbonyl, C1-4alkyloxycarbonyl, arylC1-4alkyloxycarbonyl, R5aR5bN-carbonyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, arylC1-4alkyloxyC1-4alkyl, aryloxyC1-4alkyl, pyridyl; -a1=a2-a3=a4- means a bivalent radical of formula -CH=CH-CH=CH- (c-1); where one or two hydrogen atoms in (c-1) are substituted by radical C1-6alkyl, C1-4alkoxy, halogen, hydroxy group, (R5g)(R5h)N-(C1-4alkandiyl)-O-trifluoromethyl, cyano group, radical -COOR4, (R5a)(R5b)N-sulphonyl, pyrrolidinyl-sulphonyl, piperidinyl sulphonyl, radical N(R5a)(R5b), radical (a-1), (a-7), morpholinyl, (R5g)(R5h)N-(C1-4alkandiyl)-N(R5c)-, C1-6alkylcarbonylamino, C1-6alkyloxycarbonylamino, C1-6alkylsulphonylamino, (R5a)(R5b)N-C1-4alkyl; R20 means hydrogen, spiro (C2-4alkylenedioxy), spiro (diC1-4alkyoxy) or -NR5gR5h; each R5g or R5h independently means either hydrogen, or C1-4alkyl, or R5g and R5h together with nitrogen atom whereto attached form pyrrolidinyl, piperidinyl or morpholinyl; R3 means nitro group, cyano group, amino group, halogen, hydroxy group or C1-4alkoxy; aryl means phenyl optionally substituted with one or more substitutes chosen from the group consisting of C1-6alkyl, C1-4alkoxy, halogen, hydroxy, amino and trifluoromethyl. Besides it relates to the pharmaceutical composition with antiviral activity, and method for making said compounds.

EFFECT: there are prepared and described new compounds with antiviral activity.

9 cl, 15 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a dynamic nuclear polarisation method of a compound which contains one or more carboxyl groups, distinguished by that, the radical of formula (I) , where M is one equivalent cation of an alkali metal; and R1, which are identical or different, each represents a C1-C6-alkyl group with a straight or branched chain or a -(CH2)n-X-R2 group, where n equals 1, 2 or 3; X is O; and R2 is a C1-C4alkyl group with a straight or branched chain, which are used a paramagnetic agent in the said dynamic nuclear polarisation process. The invention also relates to new radicals, to their use as paramagnetic agents.

EFFECT: obtaining new radicals of formula (I), which are used as paramagnetic agents in dynamic nuclear polarisation processes.

17 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a liquid composition which contains hyperpolarised 13C-pyruvate, involving: a) formation of a liquid mixture containing a radical of formula (I) , where M is hydrogen or one equivalent cation; and R1, which are identical or different, each represents hydroxylated and/or alkoxolated C1-C4-hydrocarbon group with a straight or branched chain, 13C-pyroracemic acid and/or 13C-pyruvate, and freezing this mixture; b) increasing polarisation of 13C nuclei of pyroracemic acid and/or pyruvate in this mixture through dynamic nuclear polarisation c) addition of a physiologically transferable buffer, which provides for pH in the range from 7 to 8, and a base to the frozen mixture for its dissolution and for converting 13C-pyroracemic acid to 13C-pyruvate, obtaining a liquid composition or, when at stage (a) only 13C-pyruvate is used, addition of a buffer to the frozen mixture for its dissolution, obtaining a liquid composition; and d) possible removal of the radical and/or its reaction products from the liquid composition. The invention also relates to use of such a composition and to a radical of formula (I).

EFFECT: obtaining a composition for use as MP of a visualising agent.

22 cl, 2 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with formula I: , where D is O; E is CH2 or O; n equals 1 or 2, and R1 is chosen from hydrogen, halogen or substituted or unsubstituted 5- or 6-member aromatic or heteroaromatic ring with 0, 1 or 2 nitrogen atoms, 0 or 1 oxygen atom, or is chosen from substituted or unsubstituted 8-, 9- or 10-member condensed heteroaromatic ring system with 0 or 1 nitrogen atom, 0 or 1 oxygen atom, where the said aromatic or heteroaromatic rings or ring systems, when they are substituted, have substitutes which are chosen from -C1-C6alkyl, -C3-C6cycloalkyl, -C1-C6alkoxy, halogen, -CF3, -S(O)mR2, where m equals 0, 1 or 2, -NR2R3, -NR2C(O)R3 or -C(O)NR2R3; R2 and R3 are in each case independently chosen from hydrogen, -C1-C4alkyl, -C3-C6cycloalkyl, aryl; or its stereoisomers, enantiomers or pharmaceutically acceptable salts; under the condition that the given compound is not 2-(1-aza-bicyclo[2.2.2]oct-3-yl)-2,3-dihydroisoindol-1-one. The invention also relates to compounds with formulae II or III, to a pharmaceutical composition, as well as to use of compounds in paragraph 1.

EFFECT: obtaining new biologically active compounds with activity towards alpha 7 nicotinic acetylcholine receptors (α7 nAChRs).

8 cl, 72 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to the new compounds of formula I in the form of the salt or zwitter-ion, wherein R1 and R3 are independently phenyl, C3-C8 cycloalkyl or thienyl group, R2 is haloid or hydroxyl group; R4 is C1-C8 alkyl substituted with -NR5-CO-R6 or -CO-NR9R10; R5 is hydrogen ; R6 is C1-C8alkyl or C1-C8 alkoxy, each of them is optionally substituted with 5- or 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R6 is 5-10-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R9 is hydrogen or C1-C8alkyl; R10 is C1-C8alkyl, optionally substituted with cyano group, C1-C8 alkoxy group or with 5- or 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R10 is 5-9-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur. The invention refers also to the pharmaceutic composition, to the application of compound of any of claims 1-5 as well as to the preparation method of compound of formula I of claim 1.

EFFECT: preparation of the new biologically active compounds taking the effect of muscarin receptor M3.

9 cl, 247 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I , in which A denotes hydrogen, B denotes methyl or B is in a trans-position relative oxygen; X denotes CH2; Y denotes a group of formula , , ,

, or ;

, in which the left-hand bond is to an oxygen atom, and the right-hand bond is to the group R; R denotes 5-indolyl; in form of a free base or an acid addition salt. The invention also relates to a pharmaceutical composition, to use of compounds in any of claims 1-7, to a method of preventing and treating psychiatric and neurodegenerative disorders in a person, as well as a method of treating and preventing diseases or pathological condition in which α7 nAChR activation plays a role.

EFFECT: obtaining novel biologically active compounds having α7 nAChR agonist activity.

16 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I

in form of a salt, where R1 and R2 each independently denotes phenyl, where one or both R1 and R2 are substituted in one, two or three positions by the following groups: halogen, C1-C8alkyl or C1-C8alkoxy, and R3 is hydroxy, or R1 and R2 each denotes an unsubstituted phenyl, and R is hydrogen, C1-C8alkyl, C1-C8alkoxy or C1-C8alkylthio, or R1 is C3-C8cycloalkyl and R2 is phenyl or a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes oxygen and sulphur, and R3 is hydroxy, or -CR1R2R3 denotes 9-hydroxy- 9H-fluoren-9-yl or 9-hydroxy-9H-xanthen-9-yl, and R4 is C1-C8alkyl substituted in one, two or three positions by a -CO-N(R5)R6 group, where R5 is hydrogen and R6 is a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes nitrogen and oxygen, optionally substituted with phenyl, or R1 and R2 each denotes an unsubstituted phenyl, and R3 is hydroxy and R4 is C1-C8alkyl substituted in one, two or three positions by a -CO-N(R5)R6 group, where R5 is hydrogen and R6 is 5-methyl-3-isoxazolyl or R1 and R2 each denote unsubstituted phenyl, and R3 is hydroxy and R4 is 1-ethyl substituted in one, two or three positions by a -CO-N(R5)R6 group, where R5 is hydrogen, R6 is a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes nitrogen and oxygen, provided that the formula I compound is not (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(pyrazin-2-ylcarbamoylmethy)-1-azoniumbicyclo[2.2.2]octane, (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(isoxazol-3-ylcarbamoylmethyl)-1-azoniumbicyclo [2.2.2]octane bromide or (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(pyrimidin-4-ylcarbamoylmethyl)-1-azoniumbicyclo [2.2.2]octane bromide. The invention also relates to a pharmaceutical composition, to use of compounds in any of claims 1-8, as well as to methods for synthesis of formula I compounds.

EFFECT: obtaining new biologically active compounds which have M3 muscarinic receptor mediated activity.

14 cl, 254 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: compounds can be used to treat diseases mediated by the nicotinic acetylcholine receptor, such as derangement of memory. In general formulae , and A is an indazolyl, benzothiazolyl or isobenzothiazolyl group which corresponds to structural formulae a) to c) respectively or X is O; R1 is H, F, Cl, Br, I, cycloalkyl containing 3-7 carbon atoms, alkoxy which contains 1-4 carbon atoms, fluorinated alkoxy which contains 1-4 carbon atoms, Ar or Het; ; R2 is H; R3 is H; R4 is H, F, Cl, Br, I, cycloalkyl which contains 3-7 carbon atoms, alkoxy which contains 1-4 carbon atoms, fluorinated alkoxy which contains 1-4 carbon atoms, Ar or Het; R5 is H; Ar is an aryl group containing 6 carbon atoms which is unsubstituted or substituted once or several times with halogen; and Het is a 5- or 6-member heteroaromatic group containing a heteroatom in the ring which is selected from N, O and S, or a 6-member saturated heterocyclic group which contains a heteroatom in the ring which is selected from N and O; and their pharmaceutically acceptable salts, where, if the said compound has formula I, the indazolyl group of group A is bonded through its 3rd, 4th or 7th position, the benzothiazole group of group A is bonded through the 4th or 7th position, the isobenzothiazole group of group A is bonded through the 3rd, 4th or 7th position.

EFFECT: obtaining compounds with properties of nicotinic acetylcholine receptor (nAChR) ligands, and pharmaceutical compositions based on the said compounds.

53 cl, 95 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula , where B represents a hydrogen atom or a group selected from -R1, -OR1, hydroxy, - O(CO)R1, cyano and non-aromatic heterocycle which is a saturated or unsaturated C3-C10carbocyclic ring in which one or more carbon atoms, preferably 1 or 2 carbon atoms, are substituted with oxygen atoms as heteroatoms, where R1 is selected from a group containing hydrogen atoms, C1-C8alkyl, C2-C8alkenyl and C3-C8cycloalkyl, where the alkyl group is unsubstituted or substituted with one or more substitutes selected from halogen atoms and C1-C4alkyl, and where the alkenyl group is unsubstituted or substituted with one or more substitutes selected from C1-C4alkyl, n equals an integer from 0 to 4, A is selected from a group containing -CH2-, -CH=CR3-, -CR3=CH-, -CR3R4-, -O-, -CO-, -O-(CH2)2-O-, where R3 and R4 each independently represents a hydrogen atom or C1-C8alkyl, m equals an integer from 0 to 8, p equals 2, and the bicyclic azonium ring contains a substitute on position 3, including all possible configurations of asymmetrical centres, D is selected from a group containing: or where R5 is selected from a group containing phenyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, R6 is selected from a group containing 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, C3-C8cycloalkyl, C1-C8alkyl, C2-C8alkenyl and phenylethyl, R7 represents a hydrogen atom or a group selected from hydroxyl, hydroxymethyl and methyl, Q represents a single bond or a group selected from -CH2-, -CH2CH2-, -O-, -O-CH2-, equals an integer from 0 to 3, X represents a pharmaceutically acceptable anion of mono- or polybasic acid, under the condition that the B-(CH2)n-A-(CH2)m- group does not represent a straight C1-4alkyl and that the following compounds are excluded: 1-allyloxycarbonylmethyl-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-azoniumbicyclo[2.2.2]octane and 1-carboxymethyl-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-azoniumbicyclo [2.2.2]octane. The invention also relates to a method of producing formula (I) compounds, to a pharmaceutical composition, to use of compounds in any of paragraphs 1-14, as well as a combined product.

EFFECT: obtaining novel biologically active compounds with antagonistic activity towards muscarine receptors M3.

21 cl, 64 ex

FIELD: medicine.

SUBSTANCE: invention is related to new compounds of formula (I): , in which: Ra and Ra', identical or different, mean atom of hydrogen or alkyl, R1 means atom of hydrogen or alkyl, cycloalkyl, heterocycloalkyl or aryl, R2 means group of formula -(CH2)x-(CO)y-Y or -(CO)y-(CH2)x-Y, in which, x = 0, 1, 2, 3 or 4, y = 0 or 1, Y means atom of hydrogen or the following group: hydroxyl, alkyl, cycloalkyl, alkyloxyl, aryl, heteroaryl or -NR11R12, besides, Y is not an atom of hydrogen, when x=y=0, R11 and R12, identical or different, mean atom of hydrogen or the following group: alkyl, cycloalkyl, alkyloxyl or -NR13R14, or R11 and R12 together with atom of nitrogen, to which they are connected, create mono- or bicyclic structure, which contains 4-10 links and unnecessarily contain additionally 1-3 heteroatoms and/or 1-3 ethylene unsaturated links, besides this cycle is not necessarily substituted in any of positions with 1-3 groups, selected from atoms of halogen and hydroxyl, alkyl, cycloalkyl and alkyloxygroups; R13 and R14, identical or different, mean atom of hydrogen or alkyl, R3 means 1-3 groups, identical or different, available in any position of cyclic structure, to which they are connected, and selected from atoms of halogen; R5 means atom of hydrogen, R4 is selected from groups of formulae (a), (b), (c), which are not necessarily substituted with aryl group, described below: (a), (b), (c), in which p=0,1,2 or 3; m=0,1 or 2, and either a) X means link -N(R10)-, in which R10 is selected from: -CO-alkyl, -CO-cycloalkyl, -CO-heterocycloalkyl, -CO-aryl, -CO-heteroaryl, - or R10 with atom of nitrogen, with which it is connected, and with atom of carbon, available in any position of cyclic structure of formula (a), but not with neighboring to mentioned atom of nitrogen, creates bridge, containing 3-5 links, or, b) X means link -C(R6)(R7)-, where R6 is selected from the following: atom of hydrogen, atom of halogen, group -(CH2)x-OR8, -(CH2)x-NR8R9, -(CH2)x-CO-NR8R9 or -(CH2)x-NR8-COR9, in which x=0,1,2,3 or 4, alkyl, cycloalkyl, heterocycloalkyl, aryl, heterocycloalkyl, condensed with aryl, besides, alkyl, cycloalkyl or aryl groups are not necessarily substituted with 1 or several groups, selected from groups: R, R', -OR, -NRR', -COR; R7 is selected from atoms of hydrogen and halogen and the following groups: alkyls, -OR, -NRR', -NR-CO-R', -NR-COOR', -R8 and R9 are selected, independently from each other, from atom of hydrogen and the following groups: alkyls, cycloalkyls, aryls, -CO-alkyls, besides, alkyls and aryls are unnecessarily substituted with one or several groups, selected from groups: R, R', -OR, or R8 and R9 together create heterocycloalkyl,- R and R' mean, independently from each other, atom of hydrogen or alkyl, cycloalkyl, besides, mentioned hetero aryl groups represent aromatic groups, including from 5 to 10 links and including from 1 to 4 heteroatoms, such as atom of nitrogen, oxygen and/or sulfur; besides mentioned heterocycloalkyl groups represent cycloalkyl groups, including from 5 to 6 links and including from 1 to 4 heteroatoms, such as atom of nitrogen, oxygen or sulfur; in the form of base or acid-additive salt, and also in the form of hydrate or solvate. Invention is also related to medicinal agent, to pharmaceutical composition, to application, to method of production, and also to compounds of formulas (VI), (XVIII), (XIX).

EFFECT: new biologically active compounds have activity of agonists of melanocortin receptors.

27 cl, 16 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of common formula (I) , in which: A, if available, means (C1-C6)-alkyl; R1 means group NR6R7, (C4-C7)-azacycloalkyl, (C5-C9)-azabicycloalkyl, besides, these groups, unnecessarily, are substituted with one or more substituents, selected from (C1-C5)-alkyl or halogen; A-R1 is such that nitrogen of radical R1 and nitrogen in position 1 of pyrazole are necessarily separated at least by two atoms of carbon; R3 means radical H, OH, NH2, ORc, NHC(O)Ra or NHSO2Ra; R4 means phenyl or heteroaryl, unnecessarily, substituted with one or more substituents, selected from halogen, CN, NH2, OH, ORc, C(O)NH2, phenyl, polyfluoroalkyl, linear or ramified (C1-C6)-alkyl, besides these substituents, unnecessarily, are substituted with halogen, and moreover, heteroaryl radicals are 3-10-member, containing one or more heteroatoms, selected from sulphur or nitrogen; R5 means radical H, linear or ramified (C1-C6)-alkyl; Ra means linear or ramified (C1-C6)-alkyl; Rc means linear or ramified (C1-C6)-alkyl, (poly)fluoroalkyl or phenyl; R6 and R7, independently from each other, means hydrogen, (C1-C6)-alkyl; R6 and R7 may create 5-, 6- or 7-member saturated or non-saturated cycle, which includes one heteroatom, such as N, and which, unnecessarily, substituted with one or more atoms of halogen; to its racemates, enantiomers, diastereoisomers and their mixtures, to their tautomers and their pharmaceutically acceptable salts, excluding 3-(3-pyridinyl)-1H-pyrazole-1- butanamine, 4-(3-pyridinyl)-1H-pyrazole-1-butanamine and N-(diethyl)-4-phenyl-1H-pyrazole-1-ethylamine. Invention is also related to methods for production of compounds of formula (I) and to pharmaceutical composition intended for treatment of diseases that appear as a result of disfunction of nicotine receptors α7 or favorably responding to their modulation, on the basis of these compounds.

EFFECT: production of new compounds and pharmaceutically acceptable composition on their basis, which may find application in medicine for treatment, prophylaxis, diagnostics and observance over development of psychiatric or neurological disorders or diseases of central nervous system, when cognitive functions deteriorate or quality of sensor information processing drops.

16 cl, 106 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with formula I: , where D is O; E is CH2 or O; n equals 1 or 2, and R1 is chosen from hydrogen, halogen or substituted or unsubstituted 5- or 6-member aromatic or heteroaromatic ring with 0, 1 or 2 nitrogen atoms, 0 or 1 oxygen atom, or is chosen from substituted or unsubstituted 8-, 9- or 10-member condensed heteroaromatic ring system with 0 or 1 nitrogen atom, 0 or 1 oxygen atom, where the said aromatic or heteroaromatic rings or ring systems, when they are substituted, have substitutes which are chosen from -C1-C6alkyl, -C3-C6cycloalkyl, -C1-C6alkoxy, halogen, -CF3, -S(O)mR2, where m equals 0, 1 or 2, -NR2R3, -NR2C(O)R3 or -C(O)NR2R3; R2 and R3 are in each case independently chosen from hydrogen, -C1-C4alkyl, -C3-C6cycloalkyl, aryl; or its stereoisomers, enantiomers or pharmaceutically acceptable salts; under the condition that the given compound is not 2-(1-aza-bicyclo[2.2.2]oct-3-yl)-2,3-dihydroisoindol-1-one. The invention also relates to compounds with formulae II or III, to a pharmaceutical composition, as well as to use of compounds in paragraph 1.

EFFECT: obtaining new biologically active compounds with activity towards alpha 7 nicotinic acetylcholine receptors (α7 nAChRs).

8 cl, 72 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to the new compounds of formula I in the form of the salt or zwitter-ion, wherein R1 and R3 are independently phenyl, C3-C8 cycloalkyl or thienyl group, R2 is haloid or hydroxyl group; R4 is C1-C8 alkyl substituted with -NR5-CO-R6 or -CO-NR9R10; R5 is hydrogen ; R6 is C1-C8alkyl or C1-C8 alkoxy, each of them is optionally substituted with 5- or 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R6 is 5-10-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R9 is hydrogen or C1-C8alkyl; R10 is C1-C8alkyl, optionally substituted with cyano group, C1-C8 alkoxy group or with 5- or 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R10 is 5-9-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur. The invention refers also to the pharmaceutic composition, to the application of compound of any of claims 1-5 as well as to the preparation method of compound of formula I of claim 1.

EFFECT: preparation of the new biologically active compounds taking the effect of muscarin receptor M3.

9 cl, 247 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns medical products and concerns the method of obtaining of a Solifenacin composition or its salts for use in a solid preparation which includes at least one stage chosen of the group consisting of (i) stage of wet granulation with use of a dissolvent for Solifenacin or its salts, thereat quantity of Solifenacin or its salts which should be dissolved in 1 ml of a dissolvent makes less than 0.1 mg, (ii) stage of dicrease of quantity or rate of addition of a dissolvent if the dissolvent moves Solifenacin or its salt in an amorphous condition, and quantity of Solifenacin or its salts which should be dissolved in 1 ml of a dissolvent 10 mg or more and (iii) stage of activisation of process of crystallisation of a composition of the wet granulation received by means of a usual way. Also the pharmaceutical composition for use in the solid preparation, showing selective opposing action against muscarinic M3 receptors is revealed.

EFFECT: rising of stability of the compositions containing Solifenacin or its salt.

12 cl, 3 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1-azabicycloalkyl of general formula I, , in which X represents CH2 or simple bond; Y represents group of formula or and, where R has values given in description, which are agonists of alpha 7 nicotine acetylcholine receptor (nAChR).

EFFECT: possibility of using as pharmaceutical preparations.

18 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to the development of a sobering agent in alcoholic intoxication. As an active agent, the agent contains meadowsweet (honeysweet) Filipendula ulmaria (L.) Maxim. herb extract prepared by dry grass extraction in boiling water taken in the ratio 1:10 for 15 minutes, and containing 2.5 g of the solids in 100 ml.

EFFECT: agent does not have adverse reactions and eliminates somatic disorders accompanying alcoholism (muscle involvement, gastrointestinal disturbances and nervous disordes).

2 ex, 2 tbl

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