SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS

The present invention relates spiro-cyclic amine derivatives 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, 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 fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms, monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen, and bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms; -Y-(C n -alkylene)-X- is a linking group wherein Y is attached to R1 and selected from a bond, -O-, -CO-, -S-, -SO-, -SO 2 -, -NH-, -CH=CH-, -C(CF 3 )=CH-, -C‰¡C-, -CH 2 -O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, and trans-cyclopropylene; n is an integer from 0 to 10; and X is attached to the phenylene/pyridyl moiety 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 fluor atoms; and R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH 2 ) 2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, -CH 2 -(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH 2 -R4 or -CO-CH 2 -R4, wherein R4 is -OH, -PO 3 H 2 , -OPO 3 H 2 , -COOH, -COO(1-4C)alkyl or tetrazol-5-yl; Q is a bond or -O-; -W-T- is selected from -CH=CH-, -CH 2 -CH 2 -, -CH 2 -O-, -O-CH 2 -, -O-CH 2 -CH 2 -, and -CO-O-; R5 is H or independently selected from one or more halogens; Z is CH, CR2 or N; and A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine; or