8-(PIPERAZIN-1-YL)-1,2,3,4-TETRAHYDRO-ISOQUINOLINE DERIVATIVES

摘要

The invention relates to compounds of Formula (I) wherein R1, R2, R3, R4 and R5 are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments, especially as modulators of the CXCR3 receptor.;

主权项

1. A compound of Formula (I)wherein
R1 represents heteroaryl-(C1-2)alkyl, wherein the heteroaryl is a 5- to 10-membered monocyclic or bicyclic aromatic ring comprising 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and or sulphur, and wherein the heteroaryl is unsubstituted or mono- or di-substituted with (C1-4)alkyl; or heterocyclyl-(C1-2)alkyl, wherein the heterocyclyl is a 5- or 6-membered monocyclic non-aromatic ring comprising one or two nitrogen atoms which is annulated to a phenyl or pyridinyl ring, and wherein the heterocyclyl is unsubstituted or mono- or di-substituted wherein the substituents are independently selected from (C1-4)alkyl or oxo; R2 represents hydrogen or methyl; R3 represents aryl, wherein the aryl is a phenyl- or naphthyl-group, which groups are independently unsubstituted or mono- or di-substituted wherein the substituents are independently selected from halogen, (C1-4)alkyl, (C1-4)alkoxy, (C1-2)fluoroalkyl, (C1-2)fluoroalkoxy or cyano; aryl-(C1-2)alkyl, wherein the aryl is a phenyl- or naphthyl-group, which groups are independently unsubstituted or mono-substituted with halogen; heteroaryl, wherein the heteroaryl is a 5- to 10-membered monocyclic or bicyclic aromatic ring comprising 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen or sulphur, and wherein the heteroaryl is unsubstituted or mono- or di-substituted wherein the substituents are independently selected from halogen, (C1-4)alkyl, (C3-6)cycloalkyl, (C1-4)alkoxy, (C1-2)fluoroalkyl, (C1-2)fluoroalkoxy, di-(C1-2)alkyl-amino, hydroxy, cyano, phenyl, pyridinyl or heteroaryl-(C1-2)alkyl, wherein the heteroaryl is a 5- or 6-membered monocyclic aromatic ring comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen or sulphur; aryl-(C1-2)alkyl-sulfonyl, wherein the aryl is a phenyl- or naphthyl-group; or R6-carbonyl; R4 represents hydrogen, halogen, (C1-2)fluoroalkyl or cyano; R5 represents hydrogen, halogen or (C1-2)fluoroalkyl; and R6 represents (C1-4)alkyl; (C3-6)cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-substituted with phenyl; (C5-6)cycloalkyl, wherein the cycloalkyl is annulated to a phenyl ring; (C1-2)alkoxy-(C1-2)alkyl; aryl, wherein the aryl is a phenyl- or naphthyl-group, which groups are independently unsubstituted or mono- or di-substituted wherein the substituents are independently selected from halogen, (C1-4)alkyl, (C1-4)alkoxy, (C1-2)fluoroalkyl and or di-(C1-2)alkyl-amino; aryl-(C1-2)alkyl, wherein the aryl is a phenyl- or naphthyl-group, which groups are independently unsubstituted or mono- or di-substituted wherein the substituents are independently selected from halogen or (C1-4)alkoxy; aryloxy-(C1-2)alkyl, wherein the aryl is a phenyl- or naphthyl-group; aryl-(C1-2)alkoxy, wherein the aryl is a phenyl- or naphthyl-group; heterocyclyl-(C1-2)alkyl, wherein the heterocyclyl is a 5- or 6-membered monocyclic non-aromatic ring comprising one or two heteroatoms independently selected from oxygen or nitrogen; heteroaryl, wherein the heteroaryl is a 5- to 10-membered monocyclic or bicyclic aromatic ring comprising 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen or sulphur, and wherein the heteroaryl is unsubstituted or mono-substituted with (C1-4)alkyl; or heteroaryl-(C1-2)alkyl, wherein the heteroaryl is a 5- to 10-membered monocyclic or bicyclic aromatic ring comprising 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen or sulphur;or a salt thereof.