Tricyclic3-piperidine, methods for their preparation and pharmaceutical composition based on them

 

The invention relates to tricyclic3-piperidinol General formula (1), where X is O or S, R1means hydrogen, halogen, C1-6alkyl or C1-4alkyloxy, Alk means C1-6alcander, a D such as defined in the claims. Also describes how to obtain the compounds of formula (1) and a pharmaceutical composition having an antagonistic activity against Central2-adrenergic receptors on the basis of these compounds. The technical result obtained new compounds possess valuable biological properties. 6 C. and 5 C.p. f-crystals, 5 tab., 17 ill.

Description text in facsimile form (see graphic part).

Claims

1. Tricyclic3-piperidine formulas (1)

its N-oxide form, pharmaceutically acceptable additive salt or a stereochemical isomeric form,

where Alk represents C1-6alcander;

n is 0 or 1;

X represents-O-, -S-;

each R1replacing the hydrogen attached to the aromatic Colley a radical of the formula

where each m is independently 0 or 1;

each Y independently represents-O-, -S-;

R2represents hydrogen;

each R4represents a halogen.

2. Connection on p. 1, where D is a radical of formula (a), (b), (C), (e), (f) or (g), where m is 1, each Y independently represents-O-, -S-.

3. The compound according to any one of paragraphs.1 and 2, where Alk represents methylene, 1,2-ethandiyl, 1,3-propandiol, 1,4-butandiol or 1.5-pentandiol.

4. Connection on p. 1, where the connection is a

5. The compound according to any one of paragraphs.1-4 used in ka the PP.1-4 to obtain the drug, designed for treatment of depression or Parkinson's disease.

7. The composition having an antagonistic activity against Central2-adrenoceptor, including pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound according to any one of paragraphs.1-4.

8. The method of obtaining the composition according to p. 7, obliquity the fact that the connection specified in any of paragraphs.1-4, as the active ingredient is thoroughly mixed with a pharmaceutically acceptable carrier.

9. A method of obtaining a connection on p. 1, characterized in that it includes N-alkylation of the intermediate compounds of formula (II)

using an alkylating reagent of formula (III)

where W1represents a suitable leaving group;

D, Alk, X, n and R1such, as defined in paragraph 1,

in an inert solvent, in the presence of a base and optionally in the presence of a catalyst and, if desired, converting compounds of formula (I) into each other by means known in the field of transformation and, further, if desired, converting compounds of formula (I) in therapeuti non-toxic salt add base by treatment with base, or, on the contrary, the conversion of an acid additive salt form into the free base by treatment with alkali or the transformation of salt add the base to the free acid by treatment with acid, and, if desirable, obtaining their stereochemical isomeric forms, or N-oxides.

10. A method of obtaining a connection on p. 1, wherein the heat that it includes the interaction of the intermediate compounds of formula (VII)

with an intermediate compound of formula (VIII)

where W1represents a suitable leaving group;

Alk, X, n, m and R1, R2and R4such, as defined in paragraph 1,

in an inert solvent, in the presence of a base and optionally in the presence of a catalyst, thus obtaining the compounds of formula (1-h)

and, if desired, converting compounds of formula (I) into each other by means known in the field of transformation and, further, if desired, converting compounds of formula (I) into a therapeutically active non-toxic acid additive salt by treatment with acid or into a therapeutically active non-toxic salt add base by treatment with base, or, narushenie salt add the base to the free acid by treatment with acid, and, if desirable, obtaining their stereochemical isomeric forms, or N-oxides.

11. A method of obtaining a connection on p. 1, characterized in that it includes reductive N-alkylation of the intermediate compounds of formula (II)

using the aldehyde derivative of formula (IV) or (IV-g)

where Alk’ represents a C1-5alcander;

p is 0 or 1;

X, Y, n and R1such, as defined in paragraph 1,

by restoring the mixture of the reactants in a suitable inert solvent, following well-known in this field techniques recovery of N-alkylation to give the compounds of formula (I) or (I-g)

and, if desired, converting compounds of formula (I) into each other by means known in the field of transformation and, further, if desired, converting compounds of formula (I) into a therapeutically active non-toxic acid additive salt by treatment with acid or into a therapeutically active non-toxic salt add base by treatment with a base, or conversely, converting the acid additive is rim acid by treatment with acid, and, if desirable, obtaining their stereochemical isomeric forms, or N-oxides.

 

Same patents:

The invention relates to new derivatives of thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione of General formula (I) or their pharmaceutically-acceptable salts, having immunosuppressive activity

The invention relates to novel condensed to thienopyrimidine formula I and their physiologically acceptable salts, having the effect of inhibitors of phosphodiesterase V(PDE V), and which can be used for the treatment of diseases of the cardiovascular system and for the treatment and/or therapy of disorders of potency

The invention relates to compounds of formula (1), where X and Y Is N or O; R1substituted alkyl, substituted arylalkyl or cycloalkyl; R2and R3Is h or alkyl; And a Is-C(O)-, -OC(O)-, -S(O)2-; R4- alkyl, cycloalkyl or (C5-C12)aryl; compounds of the formula (2), where X and Y are O, S or N; R1- alkyl, optionally substituted arylalkyl; R2and R3Is h or alkyl;- C(O)-; R6- Deputy, including the condensed heterocyclic rings; and compounds of the formula (3), where X and Y are O, S or N; R1- alkyl, alkylsilane, (C5-C12)arylalkyl, (C5-C12)aryl; R2and R3Is h or alkyl; R2' and R3' - N; R11, R12and E together form a mono - or bicyclic ring which may contain heteroatoms

The invention relates to new thienopyrimidine formula I, their pharmaceutically acceptable salts, having the effect of inhibitors of phosphodiesterase V, which can be used to combat diseases of the cardiovascular system and for the treatment and/or therapy of disorders, to pharmaceutical compositions in a form suitable for the treatment

-converting enzyme)" target="_blank">

The invention relates to novel ortho-sulfonamidophenylhydrazine heteroaryl hydroxamic acids of the formula

< / BR>
where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with

< / BR>
is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts

The invention relates to new thienopyrimidine General formula I or their physiologically acceptable salts, having the properties of an inhibitor of phosphodiesterase V, which can be used in the pharmaceutical industry for the treatment of diseases of the cardiovascular system, in particular heart failure, and for treatment of violations of a potentiality

The invention relates to sulfonamidnuyu to the compound of formula I, where R1- alkyl, alkenyl, quinil; a represents optionally substituted heterocyclic group, excluding benzimidazolyl, indolyl, 4,7-dehydrobenzperidol and 2,3-dihydrobenzofuranyl; X - alkylene, oxa, oxa(lower) alkylene; R2- optional substituted aryl, substituted biphenyl, its salts and pharmaceutical compositions comprising this compound

The invention relates to new thienopyrimidine, as well as their physiologically acceptable salts with inhibitory activity against phosphodiesterase V (PDE V), which can be used to combat diseases of the cardiovascular system and for the treatment and/or therapy of disorders of potency

The invention relates to a new 1.8-fused derivative of 2-Hinayana formula (I), where A, X, R1, R2, R3, R4, R5, R6such as defined in the claims

The invention relates to compounds which inhibit the protease encoded by human immunodeficiency virus, or their pharmaceutically acceptable salts, and such compounds are used for the prevention of infection by HIV, treating infection by HIV and the treatment of acquired as a result immunodeficiency syndrome (AIDS)

The invention relates to 3-oxo-propanenitrile derived condensed pyrazole, method of production thereof and to pharmaceutical compositions containing them

The invention relates to new derivatives of thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione of General formula (I) or their pharmaceutically-acceptable salts, having immunosuppressive activity

The invention relates to inhibitors tyrosinekinase type bis-indolylmaleimide compounds of the formula I

< / BR>
where Z denotes a group of General formula II

< / BR>
where A, B, X, Z, R1-R10have the meanings indicated in the claims, as well as the way they are received and drug based on these compounds

The invention relates to novel condensed to thienopyrimidine formula I and their physiologically acceptable salts, having the effect of inhibitors of phosphodiesterase V(PDE V), and which can be used for the treatment of diseases of the cardiovascular system and for the treatment and/or therapy of disorders of potency

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic
Up!