Monocyclic benzamide derivatives of 3 - or 4-substituted 4-(aminomethyl)piperidine derivatives, methods for their preparation, pharmaceutical composition, method of its preparation, carboxylic acid derivative

 

Describes the connection of the formula (I), its stereochemical isomeric form or its pharmaceutically acceptable additive salt of the acid or base, where R1- C1-6-alkoxy, R2is hydrogen, C1-6-alkyl, C1-C6-alkoxy, R3is hydrogen, halogen, R4is hydrogen, C1-6alkyl, R5is hydrogen, L - C3-C6cycloalkyl,2-6quinil, the radical of formula-Alk - R6(b-1), - Alk-X-R7(b-2), - Alk-Y - C(=O)-R9(b-3), - Alk-Y-C(=O)-NR11R12(b-4), where each Alk - C1-12alcander, R6is hydrogen, cyano, C1-6alkylsulfonamides,3-6cycloalkyl, Het', R7- C1-6alkyl, hydroxy, C1-6alkyl, X Is O, R9-C1-6alkyl, C1-6alkoxy, Y is a direct bond, R11and R12each independently C1-6alkyl, or R11and R12connected to the nitrogen atom bearing an R11and R12, can form pyrrolidinyl ring, Het' is selected from tetrahydrofuran, dioxolane, dioxolane, substituted C1-6the alkyl, tetrahydropyran, pyridazinyl, substituted by two substituents, each of which is independently selected from hydroxy, C1-6of alkyl, halogen; a radical (C-1), (C-3), (4), R13- C1-4-alkyl. Describes two spotka, on the basis of the compounds of formula (I) and method of preparation of the composition. Also describes monocyclic intermediate benzamide derived 3 - or 4-substituted 4 -(aminomethyl)piperidine of formula (III) and a carboxylic acid derivative of the formula (VI) to obtain the compounds of formula (I). The technical result - the use of compounds of formula (I) for the treatment of conditions associated with impaired gastric emptying. 7 C. and 6 C.p. f-crystals, 6 PL.

Description text in facsimile form (see graphic part) TC

Claims

1. Monocyclic benzamide derivatives of 3 - or 4-substituted 4-(aminomethyl)piperidine derivatives of formula (I)its stereochemical isomeric form or its pharmaceutically acceptable additive salt of the acid or base, where R1represents C1-6alkyloxy; R2represents hydrogen, C1-6alkyl or C1-6alkyloxy; R3represents hydrogen or halogen; R4represents hydrogen or C1-6alkyl; R5is hydrogen; L is C3-6cycloalkyl,2-6quinil or L is a radical of the formula
-Alk-R6(b is dstanley1-C12-alcander;
R6represents hydrogen, cyano, C1-6alkylsulfonamides,3-6cycloalkyl or Het';
R7represents C1-6alkyl, hydroxy, C1-6alkyl;
X represents O;
R9represents C1-6alkyl, C1-6alkoxy;
Y is a direct link;
R11and R12each independently represents C1-6alkyl, or R11and R12connected to the nitrogen atom bearing an R11and R12, can form pyrrolidinyl ring;
Het' is selected from tetrahydrofuran, dioxolane, dioxolane, substituted C1-6the alkyl, tetrahydropyran, pyridazinyl, substituted by two substituents, each of which is independently selected from hydroxy, C1-6the alkyl or halogen; Het' can also be a radical of formula (C-1), (C-3), (4)



R13represents C1-4alkyl.

2. Connection on p. 1, in which R1represents C1-4alkyloxy and R2represents hydrogen, C1-4alkyl or C1-4alkyloxy.

3. Connection on p. 1, in which R1represents C1-4alkyloxy and R2represents C1-4straley piperidinol part, having transconfiguration.

5. Connection on p. 1, in which OR4is located in position 4 of the Central piperidino group.

6. The compound according to any one of paragraphs. 1-4, in which L represents a C3-6cycloalkyl or2-6alkenyl, or L is a radical of formula (b-1), where each Alk represents C1-6alcander, and R6represents hydrogen, cyano, C1-6alkylsulfonamides,3-6cycloalkyl or Het', where Het' represents tetrahydrofuran, dioxolane, dioxolane, substituted C1-6the alkyl, tetrahydropyran, pyridazinyl, substituted with two substituents selected from hydroxy, halogen and C1-6the alkyl, or a radical of formula (C-1), (3) or (4) in which R13represents C1-4alkyl, or L is a radical of formula (b-2) in which Alk represents a C1-6alcander, X is O and R7represents C1-6alkyl or hydroxy, C1-6alkyl, or L is a radical of formula (b-3) in which Y represents a direct bond and R9represents C1-6alkyl or C1-6alkyloxy, or L is a radical of formula (b-4) in which Y represents a direct bond and R11and R12connected to the nitrogen atom bearing an R11and R12form PI is, associated with delayed emptying of the stomach.

8. Pharmaceutical composition for treatment of conditions associated with delayed emptying of the stomach, comprising as active ingredient a therapeutically effective amount of the compounds on p. 1 and a pharmaceutically acceptable carrier.

9. Method of preparation of pharmaceutical compositions for the treatment of conditions associated with delayed emptying of the stomach, in which a therapeutically effective amount of a compound according to any one of paragraphs. 1-6 thoroughly mixed with a pharmaceutically acceptable carrier.

10. Monocyclic benzamide derivatives of 3 - or 4-substituted 4-(aminomethyl)piperidine of formula (III)

its pharmaceutically acceptable additive salt of the acid or its stereochemical isomeric form, where R1, R2, R3, R4and R5these are, as defined in paragraph 1 for the compounds of formula (I).

11. Carboxylic acid derivative of the formula (VI)

in which R1represents methoxy;
R2is methyl;
R3is chlorine.

12. The method of obtaining the compounds of formula (I), in which an intermediate compound of formula (II) N-alkylate tamago Foundation

where W represents fluorine, chlorine, bromine, iodine, methanesulfonate, benzosulfimide or tripterocalyx, or the compound of formula (I) is converted into pharmaceutically acceptable acid additive salt.

13. The method of obtaining the compounds of formula (I), in which the corresponding ketone or aldehyde intermediate compound of formula L'= O (IV), where the specified L'= O is a compound of formula L-H in which two dual atoms of hydrogen, C1-12alkadienes fragment substituted by = O, is subjected to reaction with an intermediate compound of formula (III)

or the compound of formula (I) is converted into pharmaceutically acceptable acid additive salt.

Priority items:
11.07.1997 on PP. 1-3;
27.02.1998 on PP. 1-15.

 

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