SPIROCYCLIC AMINE DERIVATIVES AS S1P MODULATORS

申请公布号：: RU2602800(C2)
申请号：: RU20130105490
申请日期：: 2011.07.08
申请公布日期：: 2016.11.20
申请人：: EBBVI B.V.
发明人：: STOJT Aksel;IVEMA BAKKER Vauter I.;KOLEN KHejn K.A.S.;VAN DONGEN Maria J.P.;LEFLEMME Nikolas J.-L.D.;KHOBSON Edrian
分类号：: C07D265/34;A61K31/443;A61K31/5386;A61P25/00;C07D491/107
主分类号：: C07D265/34
摘要：: FIELD: pharmaceutics.SUBSTANCE: invention relates to spirocyclic amine derivatives of formula (I), where R1 is selected from cyano, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl, each of which is optionally substituted with CN or one or more fluorine atoms, (3-6C)cycloalkyl, (4-6C)cycloalkenyl or (8-10C)bicyclic group, where each of said groups is optionally substituted with halogen or (1-4C)alkyl, phenyl, optionally substituted with one or more substitutes, independently selected from halogen, (1-6C)alkyl, optionally substituted with one or more fluorine atoms, (1-6C)alkoxy, optionally substituted with one or more fluorine atoms, and (3-6C)cycloalkyl, optionally substituted with phenyl; biphenyl, optionally substituted with halogen; naphthyl; phenyl, substituted with monocyclic heterocycle; Monocyclic heterocycle, optionally independently substituted with halogen, (1-6C)alkyl, optionally substituted with one or more fluorine atoms, (3-6C)cycloalkyl or phenyl, optionally substituted (1-4C)alkyl or halogen, and bicyclic heterocycle, optionally substituted with halogen or (1-4C)alkyl, optionally substituted with one or more fluorine atoms; -Y-(C-alkylene)-X- is a binding group, where Y is bonded to R1 and is selected from a bond, -O-, -CO-, -S-, -SO-, -SO-, -CH=CH-, -C(CF)=CH-, -C≡C-, -CH-O-, -CO-NH-, -NH-CO- and trans-cyclopropylene; n is an integer between 0 and 10; and X is bonded to a phenylene group and is selected from a bond -O-, -S-, -SO-, -SO-, -NH-, -CO-, -CH=CH- and trans-cyclopropylene; R2 is H or is independently selected from one or more substitutes selected from halogen, (1-4C)alkyl, optionally substituted with one or more fluorine atoms; R3 is (1-4C)alkylene-R4, where alkylene group can be substituted with one or more halogen atoms or (CH)to form by a cyclopropyl group, or R3 is (3-6C)cycloalkylene-R4, or -CO-CH-R4, where R4 is -OH, -POH, -OPOH, -COOH, -COO(1-4C)alkyl or tetrazol-5-yl; Q is a bond; -W-T- is selected from -CH=CH-, -CH-CH-, -CH-O-, -O-CH-, -O-CH-CH- and -CO-O-; R5 is H; Z is CH, CR2 or N; and A is a morpholine ring structure or 5-, 6- or 7-member cyclic amine; or its pharmaceutically acceptable salts or one or more of its N-oxides, as well as to a method for production thereof, pharmaceutical compositions based thereon.EFFECT: said compounds have affinity to S1P receptor, and can be used for treating, relieving or preventing diseases and conditions, in which S1P receptor(s) is(are) involved.28 cl, 2 tbl, 335 ex