HEIN K.A.C. COOLEN,JACOBUS A.J. DEN HARTOG,LEONARDUS A.J.M. SLIEDREGT,MARIA J.P. VAN DONGEN,PIETER SMID,WOUTER I. IWEMA BAKKER
申请号：
BR112013000627
公开号：
BR112013000627A2
申请日:
2011.07.08
申请国别(地区):
BR
年份:
2016
代理人:
摘要：
fused heterocyclic derivatives as s1p modulators. The present invention relates to a heterocyclic derivative of the formula (I) wherein R1 is selected from cyano, (2-4c) alkenyl, (2-4c) alkynyl, (1-4c) alkyl, each substituted with cn or one. or more fluorine atoms, cycloalkyl (3-6c), cycloalkenyl (4-6c) or a bicyclic group (8-10c) each substituted with halogen or alkyl (1-4c) optionally substituted with one or more fluorine atoms phenyl, biphenyl, naphthyl, each substituted with one or more substituents independently selected from halogen, cyano, (1-4c) alkyl optionally substituted with one or more fluorine, (1-4c) alkoxy optionally substituted with one or more fluorine, amino, dimethylamino, and cycloalkyl (3-6c) atoms optionally substituted with phenyl which may be substituted with alkyl (1-4c) or halogen, and phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each substituted with (1-4c) alkyl, z is linking group - w- (cn-alkylene) -t- wherein w is attached to r1 and selected from a bond, -o-, -co-, -s-, -so-, -so-2 ~, -nh-, -ch = ch-, -c (cf-3 ~) = ch-, -c <；sym>； c-, -ch-2-o-, -o-co-, -co-o-, -co- nh-, -nh-co- and trans-cyclopropylene； n is an integer from 0 to 10； et is attached to the phenylene / pyridyl moiety and selected from a bond, -o-, -s-, -so-, -so-2-, -nh-, -co-, -c <；sym>； c-, -c <；sym>； 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 a 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 R 4 is (1-4c) -R 5 alkylene wherein one or more carbon atoms in the alkylene group may be independently substituted with one or more h
