公开(公告)号：US20130203737A1

公开(公告)日：2013-08-08

申请号：US13808908

申请日：2011-07-08

申请人： Pieter Smid ,  Wouter I. Iwema Bakker ,  Hein K.A.C. Coolen ,  Leonardus A.J.M. Sliedregt ,  Maria J.P. van Dongen ,  Jacobus A.J. den Hartog

发明人： Pieter Smid ,  Wouter I. Iwema Bakker ,  Hein K.A.C. Coolen ,  Leonardus A.J.M. Sliedregt ,  Maria J.P. van Dongen ,  Jacobus A.J. den Hartog

IPC分类号： C07D513/04 ,  C07D495/04 ,  C07D487/04 ,  C07D471/04 ,  C07D491/048 ,  C07D498/04

CPC分类号： C07D491/048 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04

摘要： The present invention relates to a fused heterocyclic derivative of the formula (I) wherein R1 is selected from cyano, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl, each optionally substituted with CN or one or more fluoro atoms, (3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, dimethylamino, and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen, and phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl, Z is a linking group —W—(Cn-alkylene)-T- wherein W is attached to R1 and selected from a bond, —O—, —CO—, —S—, —SO—, —SO2—, —NH—, —CH═CH—, —C(CF3)═CH—, —C≡C—, —CH2—O—, —O—CO—, —CO—O—, —CO—NH—, —NH—CO— and trans-cyclopropylene; n is an integer from 0 to 10; and T is attached to the phenylene/pyridyl moiety and selected from a bond, —O—, —S—, —SO—, —SO2—, —NH—, —CO—, —C═C—, —C≡C—, and trans-cyclopropylene; R2 is H or one or more substituents independently selected from cyano, halogen, (1-4C)alkyl optionally substituted with one or more halogen atoms, or (1-4C)alkoxy optionally substituted with one or more halogen atoms; ring structure A may contain one nitrogen atom; X is selected from C or N; if X is C, R3 is selected from H and (1-4C)alkyl, otherwise R3 is not present; Y is selected from NH, O and S; structure Q is a 5-, 6- or 7-membered cyclic amine; and R4 is (1-4C)alkylene-R5 wherein one or more carbon atoms in the alkylene group may independently be substituted with one or more halogen atoms or with (CH2)2 to form a cyclopropyl moiety, or R4 is (3-6C)cycloalkylene-R5, —CH2-(3-6C)cycloalkylene-R5, (3-6C)cycloalkylene-CH2-R5 or —CO—CH2-R5, wherein R5 is —OH, —PO3H2, —OPO3H2, —COOH, —COO(1-4C)alkyl or tetrazol-5-yl; or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of diseases and conditions in which (any) S1P receptor(s) is (are) involved or in which modulation of the endogenous S1P signaling system via any S1P receptor is involved.