Derivatives pyrazolylborate acid, receipt, containing pharmaceutical compositions

 

The invention relates to N-piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxamide, its pharmaceutically acceptable salt and solvate, which are strong antagonists of cannabinoid ST1-receptors. The invention also relates to a method of obtaining them, which is that the functional derivative of 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-acylpyrazolonato acid is subjected to interaction with 1-aminopiperidine in an organic solvent in the presence of a base. Thus obtained compound may turn into one of its salts or one of their solvate. In addition, the objects of the invention are intermediate alkalemia esters of 4-bromobenzoyl-2-oxopentanoic acid and intermediate alkalemia esters of 3-(4-bromobenzoyl)-2-(2-(2,4-dichlorophenyl)hydrazono)pentanol acid and a pharmaceutical composition having affinity to CB1-cannabinoid receptors. The technical result - a higher affinity for human CB1-cannabinoid receptors and the duration of the occupation CB1-cannabinoid receptors compared with the previous connections of the prior art. 5 C. and 7 C.p. f-crystals, 2 tab.

Tech 1. N-Piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4 - aripirazole-3-carboxamide formulaits pharmaceutically acceptable salt and solvate.

2. The method of obtaining N-piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxamide, its salts and solvate, characterized in that the functional derivative of 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxylic acid of the formulaprocess 1-aminopiperidine in an organic solvent and in the presence of a base; and thus obtained compound may turn into one of its salts or one of their solvate.

3. The method according to p. 2, characterized in that use functional derivative of 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxylic acid of formula (II) obtained from (C1-C6)Olkiluoto ester 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxylic acid of formula (II), which is obtained by cyclization (C1-C6)Olkiluoto ester 3-(4-bromobenzoyl)-2-(2-(2,4-dichlorophenyl)-hydrazono)pentanol acid (IX).

4. The method according to p. 3, wherein (C1-C6)alkilany ether 3-(4-bromobenzoyl)-2-(2-(2,4-dichlorophenyl)hydrazono)pentanol acid (IX) poluchennoi acid (VIII).

5. The method according to p. 4, wherein (C1-C6)alkilany ether 4-bromobenzoyl-2-oxopentanoic acid (VIII) is produced by the impact hexamethyldisilazide lithium (LiHMDS), and then (C1-C6)Olkiluoto ether 2-(1-imidazolyl)-2-octoxynol acid on bromothiophene.

6. The method according to p. 2, characterized in that use functional derivative of 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxylic acid of formula (II) obtained from (C1-C6)Olkiluoto ester 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxylic acid of formula (II), which is obtained from (C1-C6)Olkiluoto ether 4-bromobenzoyl-2-oxopentanoic acid (VIII) by means of the salt of 2,4-dichloropyridazine with subsequent cyclization.

7. Alkilany ether 4-bromobenzoyl-2-oxopentanoic acid formulawhere Alk is a (C1-C6)alkyl.

8. Alkilany ether 3-(4-bromobenzoyl)-2-(2-(2,4-dichlorophenyl)hydrazono)pentanol acid formulawhere Alk is a (C1-C6)alkyl.

9. Pharmaceutical composition having affinity for ST1-cannabinoid receptors containing as active on the standard dosage form, in which the active principle is a mixture of at least one pharmaceutical excipient.

11. Connection on p. 1 for the manufacture of medicinal products intended for the treatment of diseases involving ST1-cannabinoid receptors.

12. Connection on p. 1 for the treatment of psychotic disorders, for treating disorders of appetite and obesity, for the treatment of memory disorders and cognitive abilities; for the treatment of alcohol dependence and withdrawal syndrome tobacco.

Priority items:
01.02.1999 on PP. 1-5;
02.08.1999 on PP. 7-12;
28.01.2000 (filing date of the international application) on p. 6.

 

Same patents:

The invention relates to substituted 1-phenylpyrazol-3-carboxamide formula (Ia) in which R1xis in position 4 or 5 and denotes the group-T-CONRaRbin which T represents a direct bond or (C1-C7-alkylen; NRaRbdenotes a group selected from (a), (b), (C); R5and R6denote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8)-alkenyl or R5and R6together with the nitrogen atom to which they are linked, represent a heterocycle selected from pyrrolidine, piperidine, research, piperazine, substituted in position 4 by Deputy R9; R7denotes hydrogen, (C1-C4)-alkyl or benzyl; R8denotes hydrogen, (C1-C4)-alkyl, or R7and R8together with the carbon atom to which they are attached, form a (C3-C5-cycloalkyl; R9denotes hydrogen, (C1-C4)-alkyl, benzyl or a group-X-NR'5R'6in which R'5and R'6represent, independently from each other, (C1-C6)-alkyl; R10denotes hydrogen, (C1-C4)-alkyl; s= 0-3; t=0-3, provided that (s+t) in the same group greater than or equal to 1; the divalent radicals a and E together with the atom is which in addition, may be substituted by one or more (C1-C4-alkilani; R2xand R3xdenote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8-cycloalkyl, (C3-C8-cyclooctylmethyl provided that R2xand R3xdo not simultaneously denote hydrogen or R2xand R3xtogether form tetramethylene group; and their pharmaceutically acceptable salts

The invention relates to new compounds for combating pests, in particular derivatives carbanilide and fungicide-insecticidal tool based on them

The invention relates to pyrazole derivative of the formula I, where1means the group - NRR1R2or group-OR2, g2- g6the same or different and independently of one another denote hydrogen, halogen, C1-4alkyl, C1-4alkoxyl, trifluoromethyl, or C1-4allylthiourea; w2-w6the same or different and independently of one another denote hydrogen, halogen, C1-4alkyl, C1-4alkoxy or trifluoromethyl, provided that at least one of the substituents g2-g6and one of the substituents w2-w6different from hydrogen; R1means hydrogen or C1-4alkyl; R2- nah3-15-carbocyclic radical, unsubstituted or mono - or multiply substituted WITH1-4by alkyl; R3is hydrogen or the group CH2-R6; R4and R5each independently of one another denote hydrogen or C1-4alkyl; or R4means hydrogen and R5and w6together form an ethylene radical; R6means hydrogen, or when the deputies of the g2g3, g4, g5and/or g6different from1-4of alkyl, R6means hydrogen, C1-4alkyl or C1-5alkoxyl, and their salts

The invention relates to pyrazole derivative of the General formula I

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in which R1is phenyl, substituted cyclo(lower)alkyl, hydroxy(lower)alkyl, cyano, lower alkylenedioxy, carboxy, (lower alkoxy)carbonyl group, a lower alkanoyl, lower alkanoyloxy, lower alkoxy, phenoxy or carbamoyl, optionally substituted lower alkyl;

R2is halogen, halo(lower)alkyl, cyano, carboxy, (lower alkoxy)carbonyl group, carbamoyl, optionally substituted by alkyl;

R3is phenyl, substituted lower alkylthio, lower alkylsulfonyl, or lower alkylsulfonyl, provided that when R1is phenyl, substituted lower alkoxy, then R2represents halogen or halo(lower)alkyl,

or their pharmaceutically acceptable salts

The invention relates to pyrazole derivative of the General formula I, where g2, g3and g6hydrogen; g4- chlorine atom or bromine, WITH1-C3-alkyl, trifluoromethyl, or phenyl; g5is hydrogen or chlorine atom; w2, w3, w5and w6is hydrogen or chlorine atom; w4is hydrogen, a chlorine atom, a C1-C3-alkyl, C1-C3-alkoxy or nitro; X is a direct bond or the group -(CH2)nN(R3)-, where R3is hydrogen or C1-C3-alkyl; n is 0 or 1; R4is hydrogen or C1-C3-alkyl and, when X is a direct bond, R is a group-NR1R2where R1is hydrogen, C1-C6-alkyl or cyclohexyl, and R2- C1-C6-alkyl, non-aromatic carbocyclic radical WITH3-C15possibly substituted by a hydroxyl group, one or more1-C5-alkilani,1-C5alkoxygroup or halogen; amino group WITH1-C4-alkyl in which the amino may dazamide1-C3-alkyl, cyclohexyl1-C3-alkyl; phenyl, unsubstituted or substituted with halogen, or WITH1-C5-alkyl; phenyl WITH1-C3-alkyl, diphenyl1-C3-Olinala, hinokitiol and oxybutylene, unsubstituted or substituted C1-C3-alkyl or benzyl; 1-adamantaneacetic; C1-C3-alkyl, substituted aromatic heterocycle selected from pyrrolyl, pyridyl or indolyl, unsubstituted or substituted C1-C5-alkyl, or R1and R2form together with the nitrogen atom to which they relate, pyrrolidinyl, piperidyl or morpholinyl; or the group R5that represents phenyl WITH1-C3-alkyl, unsubstituted or substituted C1-C5-alkyl; cyclohexyl1-C3-alkyl, or 2-norbornylene; when X represents a group -(CH2)nN(R3)-, R represents a group R2Athat represents a non-aromatic carbocyclic radical WITH3-C15; phenyl substituted by halogen; phenyl WITH1-C3-alkyl, possibly substituted with halogen; indolyl, possibly substituted C1-C5alkoxygroup; anthracene, or group with other2bin which R2b- cyclohexyl, substituted, phenyl, unsubstituted or substituted by one or two halogen atoms, WITH1-C5-alkyl or C1-C5alkoxygroup or their acid additive salts

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-methoxykynuramine acids" target="_blank">

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