2-aniline-4-aryl substituted thiazole derivatives

Patent metadata

Field	Value
Publication number	US-9388175-B2
Application number	US-6368908-A
Country	US
Kind code	B2
Filing date	Feb 13, 2008
Priority date	Sep 13, 2005
Publication date	Jul 12, 2016
Grant date	Jul 12, 2016

Abstract

This invention concerns the use of a compound of formula (I)

a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein
Z is hydrogen, halo, C 1-6 alkyl, Het 1 , HO—C 1-6 alkyl-, cyano-C 1-6 alkyl-, amino-C(═O)—C 1-6 alkyl-, formylamino-C 1-6 alkyl-, C 1-6 alkyl-C(═O)—NH—C 1-6 alkyl-, mono- or di(C 1-6 alkyl)amino-C(═O)—C 1-6 alkyl-, phenyl-C 1-6 alkyl-, or Het 4 -C 1-6 alkyl-;
Q is phenyl, pyridyl, benzofuranyl, 2,3-dihydro-benzofuranyl, pyrazolyl, isoxazolyl or indazolyl wherein each of said ring systems is optionally being substituted with up to three substituents each independently selected from halo, cyano, C 1-6 alkyl, C 1-6 alkyl-O—, C 1-6 alkylthio, Ar or polyhaloC 1-6 alkyl;
L is phenyl, pyridyl, pyrimidazolyl, 8-Azapyrimidazolyl, pyridazinyl, imidazothiazolyl or furanyl wherein each of said ring systems may optionally be substituted with one or two or more substituents, each substituent independently being selected from halo, hydroxy, amino, cyano, C 1-6 alkyl or C 1-6 alkyl-O—;
Het 1 represents morpholinyl; pyrazolyl or imidazolyl;
Het 4 represents morpholinyl, pyrazolyl or imidazolyl;
Ar represents phenyl optionally substituted with halo, C 1-6 alkyl, C 1-6 alkyl-O— or polyhaloC 1-6 alkyl; for the manufacture of a medicament for the prevention or the treatment or prophylaxis of psychotic disorders, intellectual impairment disorders or diseases or conditions in which modulation of the α7 nicotinic receptor is beneficial.

First claim

The invention claimed is:

1. A compounds of formula

a pharmaceutically acceptable addition salt, or a stereochemically isomeric form thereof, wherein
n is 0, 1, 2, 3 or 4;
m is 0, 1, 2, 3 or 4;
R 1 each independently represents halo; hydroxy; C 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkylthio; C 1-6 alkyloxycarbonyl; polyhaloC 1-6 alkyl-O— or polyhaloC 1-6 alkyl;
R 2 each independently represents halo; hydroxy; amino; cyano; mono- or di(C 1-6 alkyl)amino; C 1-6 alkyl; HO—C 1-6 alkyl-; amino-C 1-6 alkyl-; HO—C(═O)—C 1-6 alkyl-; polyhaloC 1-6 alkyl; C 1-6 alkyl-O—; C 1-6 alkylthio; C 1-6 alkyl-O—C(═O)—; aminocarbonyl; polyhaloC 1-6 alkyl-O— or C 1-6 alkyl-C(═O)—NH—;
Z is; C 1-6 alkyl-C(═O)—NH—C 1-4 alkyl-;
C 3-6 cycloalkyl-C(═O)—NH—C 1-4 alkyl-; formylamino-C 1-4 alkyl-; Ar 4 —C 1-4 alkyl-; R x R y N—C(═O)—C 1-4 alkyl-;
C 1-6 alkyl-O—C 1-6 alkyl; C 1-6 alkyl-C(═O)—NH—C 1-6 alkyl; C 1-6 alkyl-S(═O) 2 —NH—C 1-6 alkyl;
Het 5 -C(═O)—NH—C 1-6 alkyl; Ar 5 —C(═O)—NH—C 1-6 alkyl or Z represents C 1-6 alkyloxy-C(═O)—C 2-4 alkyl-;

Het 5 represents isoxazolyl or pyridyl wherein each of said ring systems may optionally be substituted with up to 3 substituents, each substituent independently being selected from halo or C 1-6 alkyl;
Ar 4 represents phenyl optionally substituted with halo, C 1-6 alkyl, C 1-6 alkyloxy, polyhaloC 1-6 alkyloxy or polyhaloC 1-6 alkyl;
Ar 5 represents phenyl optionally substituted with halo, C 1-6 alkyl, C 1-6 alkyloxy, polyhaloC 1-6 alkyloxy or polyhaloC 1-6 alkyl;
R x and R y each independently represent hydrogen, C 1-6 alkyl, C 1-6 alkyl-O—C 1-6 alkyl or R x and R y taken together with the N atom to which they are attached form a 5 or 6 membered heterocycle selected from pyrrolidinyl, thiomorpholinyl, piperidinyl or morpholinyl.

2. A compound according to claim 1 wherein;
n is 0, 1, 2, 3 or 4;
m is 0, 1, 2, 3 or 4;
R 1 each independently represents halo; hydroxy; C 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkylthio; C 1-6 alkyloxycarbonyl; polyhaloC 1-6 alkyl-O— or
polyhaloC 1-6 alkyl;

R 2 each independently represents, halo; hydroxy; amino; cyano; mono- or di(C 1-6 alkyl)amino; C 1-6 alkyl; HO—C 1-6 alkyl-; amino-C 1-6 alkyl-; HO—C(═O)—C 1-6 alkyl-; polyhaloC 1-6 alkyl; C 1-6 alkyl-O—; C 1-6 alkylthio; C 1-6 alkyl-O—C(═O)—; aminocarbonyl; polyhaloC 1-6 alkyl-O— or C 1-6 alkyl-C(═O)—NH—;
Z is; C 1-6 alkyl-C(═O)—NH—C 1-4 alkyl-;
C 3-6 cycloalkyl-C(═O)—NH—C 1-4 alkyl-; formylamino-C 1-4 alkyl-; Ar 4 —C 1-4 alkyl-; R x R y N—C(═O)—C 1-4 alkyl-; or Z represents C 1-6 alkyloxy-C(═O)—C 2-4 alkyl-;

Ar 4 represents phenyl optionally substituted with halo, C 1-6 alkyl, C 1-6 alkyloxy or polyhaloC 1-6 alkyl;
R x and R y each independently represent hydrogen, C 1-6 alkyl or R x and R y taken together with the N atom to which they are attached form a 5 or 6 membered heterocycle selected from pyrrolidinyl, thiomorpholinyl, piperidinyl or morpholinyl.

3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1 or 2 .

4. A process of preparing a composition as claimed in claim 3 characterized in that a pharmaceutically acceptable carrier is intimately mixed with a therapeutically effective amount of a compound as claimed claim 1 or 2 .

Assignees

• Thuring Johannes Wilhelmus John F
• Macdonald Gregor James
• Grantham Christopher James
• Dinklo Theodorus
• Lesage Anne Simone Josephine
• Janssen Pharmaceutica Nv

Inventors

• Thuring Johannes Wilhelmus John F
• Macdonald Gregor James
• Grantham Christopher James
• Dinklo Theodorus
• Lesage Anne Simone Josephine

Classifications

• A61P43/00

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

• A61P25/24

  Antidepressants · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title