Urea and amide derivatives of aminoalkylpiperazines and use thereof

Patent metadata

Field	Value
Publication number	US-9598387-B2
Application number	US-201314434202-A
Country	US
Kind code	B2
Filing date	Oct 11, 2013
Priority date	Oct 11, 2012
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

Provided are compounds represented by the formula: with Y, Ri, and R2 being defined in the present disclosure; pharmaceutically acceptable salts thereof, deuterated forms thereof, isomers thereof, solvates thereof, and mixtures thereof. The compounds can be used for treating a patient suffering from a condition capable of treatment with a partial agonist or antagonist of the dopamine D2/D3 receptors and are especially useful for patients suffering from schizophrenia, depressions, neurodegenerative diseases such as Parkinson's, dyskinesias, substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol, glaucoma, cognitive disorders, restless leg syndrome, attention deficit hyperactivity disorders, hyperprolactinemia, autism, motor disturbances such as akathisia, rigor, dystonias as well as various disorders of the urinary tract and other neurologic disorders. Also provided are processes for the preparation of compounds of the present disclosure.

First claim

What is claimed is:

1. A compound represented by following formula (I)

In which:
Y is an unbranched, saturated or unsaturated hydrocarbon chain with 2-5 carbon atoms
R 1 =is a heterocycle selected from the group consisting of pyrimidyl optionally substituted with at least one member selected from the group consisting of branched or straight chained alkyl group containing 1-6 carbon atoms, cyclopropyl, halo selected from the group consisting of Cl, F and Br, trifluoromethyl; and 2- or 4-quinolinyl optionally substituted with at least one member selected from the group consisting of branched or straight chained alkyl group containing 1-6 carbon atoms, halo and trifluoromethyl;
R 2 =cyclohexyl, 4-phenyl cyclohexyl, 1-substituted piperidine-4-yl, wherein the piperidine-4-yl is substituted with a member selected from the group consisting of phenyl and benzyl, or an imidazo(1,2-a)azine-2-yl, wherein the azine is selected from the group consisting of pyridine, pyrimidine, pyrazine and pyridazine; wherein the imidazo(1,2-a)azinyl is optionally substituted with at least one member selected from the group consisting of a straight chained alkyl group, wherein the alkyl contains 1-6 carbon atoms;
pharmaceutically acceptable salts thereof, optical isomers thereof, solvates thereof, and mixtures thereof.

2. A compound selected from the group consisting of:
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-4-phenylcyclohexanecarboxamide,
4-Phenyl-N-(4-(4-(quinolin-4-yl)piperazin-1-yl)butyl)cyclohexanecarboxamide,
N-(4-(4-(7-Chloroquinolin-4-yl)piperazin-1-yl)butyl)-4-phenylcyclohexanecarboxamide,
4-Phenyl-N-(4-(4-(quinolin-2-yl)piperazin-1-yl)butyl)cyclohexanecarboxamide,
N-(4-(4-(2-(tert-Butyl)-6-methylpyrimidin-4-yl)piperazin-1-yl)butyl)-1-(5-(trifluoromethyl)pyridin-2-yl)piperidine-4-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-1-phenylpiperidine-4-carboxamide,
1-Benzyl-N-(4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)piperidine-4-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-1-(5-(trifluoromethyl)pyridin-2-yl)piperidine-4-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-methylpyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-cyclopropylpyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyrimidine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyrazine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-6-chloroimidazo[1,2-b]pyridazine-2-carboxamide,
N-(4-(4-(Quinolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(7-Chloroquinolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-5-(hydroxymethyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-3-((dimethylamino)methyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-5-((dimethylamino)methyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2,6-Di-tert-butylpyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(tert-Butyl)quinazolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(7-(Trifluoromethyl)quinolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(6-(tert-Butyl)-2-methylpyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(Quinolin-2-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyrimidine-2-carboxamide,
N-(4-(4-(Quinazolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
3-Bromo-N-(4-(4-(quinolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
3-Chloro-N-(4-(4-(quinolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide,
N-(4-(4-(2-(Trifluoromethyl)quinolin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide;
pharmaceutically acceptable salt thereof, solvate thereof and mixtures thereof.

3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 1 , pharmaceutically acceptable salt thereof, optical isomers thereof, and/or solvate thereof.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 2 , pharmaceutically acceptable salt thereof, solvate thereof and mixtures thereof.

5. The compound according to claim 2 , being N-(4-(4-(2-(tert-Butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)imidazo[1,2-a]pyridine-2-carboxamide; a pharmaceutically acceptable salt thereof, solvate thereof and mixtures thereof.

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 5 , pharmaceutically acceptable salt thereof, solvate thereof and mixtures thereof.

7. The compound according to claim 1 , wherein Y is butyl.

8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 7 , pharmaceutically acceptable salt thereof, optical isomers thereof, solvate thereof and mixtures thereof.

Assignees

• Southern Res Inst

Inventors

• Ananthan Subramaniam

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title