Heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators

摘要

The present invention relates to phenyl-substituted heterocyclyl derivatives of the formula (I),;
wherein Z, n, m, R1, R2, R3, R4, R5, R6, R7 and R8 are as described in the description and their use as prostaglandin receptor modulators, most particularly as prostaglandin D2 receptor modulators, in the treatment of various prostaglandin-mediated diseases and disorders, to pharmaceutical compositions containing these compounds and to processes for their preparation.

主权项

1. A compound of formula (I):wherein
R1 represents hydrogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)fluoroalkyl, (C1-C4)alkylsulfonyl, halogen or cyano; R2 represents hydrogen or halogen; one of R3, R4 and R5 represents carboxy-(C1-C3)alkyl, carboxy-cyclopropyl or carboxy-(C1-C3)alkoxy and the other two represent independently of each other hydrogen, (C1-C4)alkoxy or halogen; R6 represents hydrogen, (C1-C4)alkoxy or halogen; R7 represents hydrogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C3-C6)cycloalkyl-methoxy, (C3-C6)cycloalkyloxy, methoxy-ethoxy, di-[(C1-C2)alkyl]-amino, (C1-C4)fluoroalkyl, (C1-C4)fluoroalkoxy, halogen or (C1-C4)alkylsulfonyl; or R6 and R7 together represent methylendioxy or ethylendioxy; R8 represents
(C2-C5)alkyl;(C1-C5)alkyl which is mono- or di-substituted wherein the substituents are independently selected from hydroxy, (C1-C4)alkoxy, oxo, —NR9R10, optionally substituted (C3-C6)cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted aryloxy, optionally substituted heteroaryloxy or optionally substituted aryl-(C1-C2)alkoxy;(C3-C5)alkenyl;(C2-C3)alkenyl which is mono-substituted with optionally substituted aryl or optionally substituted heteroaryl;(C3-C5)alkynyl;(C3-C6)cycloalkyl which is unsubstituted, mono-, di-, tri- or tetra-substituted with methyl; mono-substituted with oxo; mono-substituted with optionally substituted aryl; or mono-substituted with optionally substituted heteroaryl; orheterocyclyl which is optionally mono-substituted with oxo; R9 represents (C1-C4)alkyl; R10 represents optionally substituted diphenylmethyl; n represents 1 or 2; m represents 1 or 2; and Z represents —NH—, —O— or a bond; or a salt thereof.