A derivative of 2-aryl-8-oxopiperidine, method thereof, pharmaceutical composition and means containing, intermediate connection

 

The invention relates to new derivatives of 2-aryl-8-oxopiperidine formula (I) having a selective affinity towards BZw3receptor, the method thereof, pharmaceutical composition and means containing it, and also to the intermediate compound of formula (II) to obtain the derivatives of 2-aryl-8-oxopiperidine. In the compounds of formula (I), W represents a hydrogen atom, a lower alkyl group, halogen atom, lower alkoxygroup, amino group, mono - or di-lower alkylamino or either unsubstituted or substituted by trifluoromethyl phenyl group; X represents a hydrogen atom, a lower alkyl group, cycloalkyl-lower alkyl group, a phenyl-lower alkyl group, lower alkenylphenol group, karbamoilnuyu group, di-lower alkylcarboxylic group or a group of formula (Q) -CH(R3)SOP(R1)(R2), where R1represents a lower alkyl group, lower alkenylphenol group, cycloalkyl group, cycloalkyl-lower alkyl group or a hydroxy-lower alkyl group, R2represents a lower alkyl group, cycloalkyl group, phenyl group, unsubstituted or substituted with halogen, lower alkoxy or Hydra is sup>1and R2can be combined with the adjacent nitrogen atom with the formation of piperidino rings, pyrolidine ring, morpholino rings or piperazinovogo rings, and these rings may be optionally substituted by one or two lower alkyl groups, and R3represents a hydrogen atom, a lower alkyl group or a hydroxy-lower alkyl group), Y represents a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group or a group of formula (Q), above, and a represents a phenyl group, unsubstituted or substituted with halogen, lower alkyl, nitro, lower alkoxy, trifluoromethyl or hydroxy, or an unsubstituted heteroaryl group selected from pyridyl, tanila or furil. In the compounds of formula (II), W represents a hydrogen atom, a lower alkyl group, halogen atom, lower alkoxygroup, phenyl group, unsubstituted or substituted by trifluoromethyl, Y2represents a hydrogen atom, a lower alkyl group, or phenyl-lower alkyl group and a represents a phenyl group, unsubstituted or substituted with halogen, lower alkyl, nitro, lower alkoxy, trifluoromethyl or hydroxy, or an unsubstituted heteroaryl the political means for the treatment of diseases, associated with the alarm condition. 9 C. and 6 C.p. f-crystals, 25 PL.

Description text in facsimile form (see graphic)g

Claims

1. A derivative of 2-aryl-8-oxopiperidine the following formula (I):

where W represents a hydrogen atom, a lower alkyl group, halogen atom, lower alkoxygroup, amino group, mono - or di-lower alkylamino or either unsubstituted or substituted by trifluoromethyl phenyl group;

X represents a hydrogen atom, a lower alkyl group, cycloalkyl-lower alkyl group, a phenyl-lower alkyl group, lower alkenylphenol group, karbamoilnuyu group, di-lower alkylcarboxylic group or a group of formula (Q)

-CH(R3)CON(R1)(R2), (Q)

where R1represents a lower alkyl group, lower alkenylphenol group, cycloalkyl group, cycloalkyl-lower alkyl group or a hydroxy-lower alkyl group;

R2represents a lower alkyl group, cycloalkyl group, phenyl group, unsubstituted or substituted haloge the m alkoxy or hydroxy, or R1and R2can be combined with the adjacent nitrogen atom with the formation of piperidino rings, pyrolidine ring, morpholino rings or piperazinovogo rings, and these rings may be optionally substituted by one or two lower alkyl groups;

R3represents a hydrogen atom, a lower alkyl group or a hydroxy-lower alkyl group),

Y represents a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group or a group of formula (Q)

-CH(R3)CON(R1)(R2), (Q)

(where R1, R2and R3are as defined above);

Rather it represents a phenyl group, unsubstituted or substituted with halogen, lower alkyl, nitro, lower alkoxy, trifluoromethyl or hydroxy, or an unsubstituted heteroaryl group selected from pyridyl, tanila or furil,

provided that when one of X and Y in the above formula (I) represents a group of formula (Q), then the other represents the same groups for X or Y, as described above, with the exception of the group of formula (Q) or its pharmaceutically acceptable salt of the added acid.

2. Connection on p. 1, where a represents a group of formula (A’):

pyridyloxy group, thienyl group or follow group.

3. The compound according to any one of paragraphs.1 and 2, where

(a) X represents a group of formula (Qx):

-CH(R31)SOP(R11)(R21), (Qx)

where R11represents a lower alkyl group and R21represents a lower alkyl group or a group of formula (A’)

(where R4represents a hydrogen atom, halogen atom, lower alkoxygroup or hydroxy-group;

R5represents a hydrogen atom;

m is 0, 1 or 2),

or R11and R21can be combined with the adjacent nitrogen atom with the formation of piperidino rings, pyrolidine ring, morpholino rings or piperazinovogo rings, and these rings may be optionally substituted by one or two lower alkyl groups;

R31represents a hydrogen atom, a lower alkyl group or a hydroxy-lower alkyl group;

Y represents a hydrogen atom or a lower alkyl group,

or (b) X represents a hydrogen atom, a lower alkyl group is (Qy)

where R11, R21and R31are as defined above.

4. Connection on p. 3, where

(a) X represents a group of the above formula (Qx) (where R11represents a methyl group, ethyl group, through the group, isopropyl group or boutelou group, R21represents an ethyl group, through the group, isopropyl group, boutelou group, phenyl group or phenyl group substituted with halogen, methoxy or hydroxy, benzyl group or benzyl group, samewindow halogen, methoxy or hydroxy, and R31is as defined in paragraph (3), and Y represents a hydrogen atom, methyl group or ethyl group,

or (b) X represents a hydrogen atom, methyl group, ethyl group, through the group, isopropyl group or boutelou group;

Y represents a group of the above formula (Qy) (where11represents a methyl group, ethyl group, through the group, isopropyl group or boutelou group, R21represents an ethyl group, through the group, isopropyl group, boutelou group, phenyl group, phenyl group, samewindow halogen, methoxy elisetta such as defined in paragraph (3).

5. A derivative of 2-aryl-8-oxopiperidine formula (Ia)

where R12and R22are the same or different and each represents an ethyl group, through group or boutelou group, or R12represents a methyl group, ethyl group or through group, R22represents a phenyl group, halogenfrei group, metoksifenilny group, benzyl group, halogenmethyl group or methoxybenzyloxy group, R32represents a hydrogen atom, methyl group or ethyl group, Y1represents a hydrogen atom, methyl group or ethyl group, and R41represents a hydrogen atom, halogen atom, methyl group, methoxy group, a nitrogroup, or triptorelin group,

or its pharmaceutically acceptable salt of the added acid.

6. Connection on p. 5, where R32represents a hydrogen atom.

7. A derivative of 2-aryl-8-oxopiperidine formula (Ib)

where X1represents a hydrogen atom, methyl group, ethyl group, or through the group;

R12and R22are Odin and R12represents a methyl group, ethyl group or through group and R22represents a phenyl group, halogenfrei group, metoksifenilny group, benzyl group, halogenmethyl group or methoxybenzyloxy group, R32represents a hydrogen atom, methyl group or ethyl group, and R41represents a hydrogen atom, a halogen atom, a metal group, a methoxy group, a nitrogroup, or triptorelin group,

or its pharmaceutically acceptable salt of the added acid.

8. Connection on p. 7, where R32represents a hydrogen atom.

9. Connection on p. 1, selected from the following compounds:

8,9-dihydro-9-methyl-N-methyl-8-oxo-2-phenyl-N-phenyl-7H-purine-7-ndimethylacetamide,

8,9-dihydro-2-(4-forfinal)-9-methyl-N-methyl-8-oxo-N-phenyl-7H-purine-7-ndimethylacetamide,

N-ethyl-6,9-dihydro-2-(4-forfinal)-9-methyl-8-oxo-N-phenyl-7H-purine-7-ndimethylacetamide,

7,8-dihydro-7-methyl-8-oxo-2-phenyl-N,N-dipropyl-N-purine-9-ndimethylacetamide,

7-ethyl-7,8-dihydro-8-oxo-2-phenyl-N,N-dipropyl-N-purine-9-ndimethylacetamide,

N-ethyl-8,9-dihydro-9-methyl-8-oxo-2-phenyl-N-phenyl-7H-purine-7-ndimethylacetamide,

N-benzyl-7,8-dihydro-N-methyl-7-methyl-8-oxo-2-phenyl-N-purine-9-ndimethylacetamide,

N-benzyl-N-ethyl-7,8-dihydro-7-methyl-8-oxo-2-(4-chlorphen the pharmaceutically acceptable salt of the added acid.

10. N-Benzyl-N-ethyl-7,8-dihydro-7-methyl-8-oxo-2-phenyl-N-purine-9-ndimethylacetamide or its pharmaceutically acceptable salt of the added acid.

11. The method of obtaining the derivative of 2-aryl-8-oxopiperidine formula (I) under item 1, where X represents a hydrogen atom and Y represents a group of formula (Q), by reacting the compounds of formula (IV):

where Y3represents the aforementioned group of formula (Q) and a and W are as defined in paragraph 1,

with azide compound and, if necessary, subsequent removal of the protective groups of the product; and, if necessary, converting the thus obtained product in its pharmaceutically acceptable salt of the added acid.

12. Pharmaceutical composition having selective affinity towards BZw3the receptor, which contains as active ingredient a derivative of 2-aryl-8-oxopiperidine specified in any of paragraphs.1-10, or its pharmaceutically acceptable salt of the added acid.

13. The tool that has anti-anxiety (anxiolytic) activity for the treatment of diseases associated with anxiety States, which contains as active ingredient a derivative of 2-aryl-8/p>14. Anxiolytic agent, which contains as active ingredient a derivative of 2-aryl-8-oxopiperidine specified in any of paragraphs.1-10, or its pharmaceutically acceptable salt dobavleniyami.

15. A derivative of 2-aryl-8-oxopiperidine formula (II)

where W represents a hydrogen atom, a lower alkyl group, halogen atom, lower alkoxygroup, phenyl group, unsubstituted or substituted by trifluoromethyl, Y2represents a hydrogen atom, a lower alkyl group or phenyl-lower alkyl group and a represents a phenyl group, unsubstituted or substituted with halogen, lower alkyl, nitro, lower alkoxy, trifluoromethyl or hydroxy, or an unsubstituted heteroaryl group selected from pyridyl, tanila or furil, as an intermediate product to obtain the derivatives of 2-aryl-8-oxopiperidine.

 

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or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,

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< / BR>
or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,

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The invention relates to arylpiperazines General formula I

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where is phenyl, pyridyl or pyrimidyl; each R3- H, halogen, NO2, СООR, where R is H, C1-6alkyl, CN, CF3WITH1-6alkyl, -S - C1-6alkyl, -SO-Cl - C1-6alkyl, -SO2-Cl-C1-6alkyl, C1-6alkoxy and up to10aryloxy, n= 1, 2, or 3; R is a direct bond; And - piperazinil, X1and X2IS N; Y IS-SO2-; Z IS - N(OH)-CHO; Q - CH2-; R1- H, C1-6alkyl, C5-7cycloalkyl until10aryl, until10heteroaryl until1-2aralkyl or until12heteroallyl, R4- H, C1-6alkyl, and others; R2- H, C1-6alkyl, or together with R1- carbocyclic or heterocyclic Spiro 5-, 6 - or 7-membered ring containing at least one heteroatom selected from N, O or S, and the group Q can be associated either with R1or R2with the formation of 5,- 6 - or 7-membered alkyl or heteroalkyl ring that includes one or more O, S or N

The invention relates to new derivatives of phenylsulfonylacetate General formula (I), which are herbicide and regulating plant growth properties and can find application in agriculture
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