AXEL STOIT,HEIN K.A.C. COOLEN,MARIA J.P. VAN DONGEN,NICOLAS J.-L.D. LEFLEMME,WOUTER I. IWEMA BAKKER
申请号：
BR112013000629
公开号：
BR112013000629A2
申请日:
2011.07.08
申请国别(地区):
BR
年份:
2016
代理人:
摘要：
spiro-cyclic amine derivatives as s1p modulators. The present invention relates to the spiro-cyclic amine derivatives of 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 fluorine atoms, (3-6c) cycloalkyl, (4-6c) cycloalkenyl or a (8-10c) bicyclic group each optionally substituted with halogen or (1-4c) alkyl, phenyl, biphenyl naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6c) alkyl optionally substituted with one or more fluorine atoms, (1-6c) alkoxy optionally substituted with one or more fluorine atoms optionally phenyl substituted amino, di (1-4c) alkylamino and (3-6c) cycloalkyl which may be substituted with (1-4c) alkyl or halogen, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocide each one optionally substituted with (1-4c) alkyl optionally substituted with one or more fluorine atoms, optionally independently substituted halogenated monocyclic heterocycle, (1-6c) alkyl optionally substituted with one or more fluorine atoms, (3-6c) cycloalkyl, or optionally substituted with (1-6c) phenyl 4c) alkyl or halogen, and bicyclic heterocycle optionally substituted with halogen or (1-4c) alkyl optionally substituted with one or more fluorine atoms； -y- (C n -alkylene) -x- is a bonding group wherein y is bonded 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； ex is bonded to the phenylene / pyridyl component and selected from a bond, -o-, -s-, -so-, -so-2-, -nh-, -co-, -ch = ch-, and trans cyclopropylene； R2 is h or independently selected from one or more substituents selected from halogen, (1-4c) alkoxy and (1-4c) alkyl optionally substituted with one or more fluorine atoms； and R3 is (1-4c) alkylene-R4 wh
