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1. 发明专利

DK2590955T3 SPIRO-CYKLISKE AMINDERIVATER SOM S1P-MODULATORER 未知
公开(公告)号：DK2590955T3
公开(公告)日：2016-12-05
申请号：DK11730314
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： STOIT AXEL , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , VAN DONGEN MARIA J P , LEFLEMME NICOLAS J -L D , HOBSON ADRIAN D
IPC分类号： C07D265/36 , A61K31/407 , A61K31/4355 , A61K31/5386 , A61P25/00 , C07D491/107 , C07D491/20

2. 发明专利

AU2011275760B2 Spiro-cyclic amine derivatives as S1P modulators 未知
公开(公告)号：AU2011275760B2
公开(公告)日：2015-08-13
申请号：AU2011275760
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： STOIT AXEL , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , VAN DONGEN MARIA J P , LEFLEMME NICOLAS J L D , HOBSON ADRIAN D
IPC分类号： C07D265/36 , A61K31/407 , A61K31/4355 , A61K31/5386 , A61P25/00 , C07D491/107 , C07D491/20
摘要： The present invention relates spiro- cyclic amine derivatives of the formula (I) wherein R1; R2; R3; Q; -W-T-; R5; Z; and A have the definitions provided in the claims; 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 (a) S1P receptor (s) is (are) involved.

3. 发明专利

ES2606137T3 Derivados de aminas espirocíclicas como moduladores de S1P 未知
公开(公告)号：ES2606137T3
公开(公告)日：2017-03-22
申请号：ES11730314
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： STOIT AXEL , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , VAN DONGEN MARIA J P , LEFLEMME NICOLAS J -L D , HOBSON ADRIAN D
IPC分类号： C07D265/36 , A61K31/407 , A61K31/4355 , A61K31/5386 , A61P25/00 , C07D491/107 , C07D491/20
摘要： Un derivado de amina espiro-cíclica de la fórmula (I)**Fórmula** en donde R1 se selecciona de ciano, (2-4C)alquenilo, (2-4C)alquinilo, (1-4C)alquilo cada uno opcionalmente sustituido con CN o uno o más átomos de fluoro, (3-6C)cicloalquilo, (4-6C)cicloalquenilo o un grupo (8-10C)bicíclico, cada uno opcionalmente sustituido con halógeno o (1-4C)alquilo, fenilo, bifenilo, naftilo, cada uno opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente de halógeno, ciano, (1-6C)alquilo opcionalmente sustituido con uno o más átomos de fluoro, (1-6C)alcoxi opcionalmente sustituido con uno o más átomos de fluoro, amino, di(1-4C)alquilamino y (3- 6C)cicloalquilo opcionalmente sustituido con fenilo que puede estar sustituido con (1-4C)alquilo o halógeno, fenilo sustituido con fenoxi, bencilo, benciloxi, feniletilo o heterociclo monocíclico, cada uno opcionalmente sustituido con (1-4C)alquilo opcionalmente sustituido con uno o más átomos de fluoro, heterociclo monocíclico opcionalmente independientemente sustituido con halógeno, (1-6C)alquilo opcionalmente sustituido con uno o más átomos de fluoro, (3-6C)cicloalquilo, o fenilo opcionalmente sustituido con (1-4C)alquilo o halógeno, y heterociclo bicíclico opcionalmente sustituido con halógeno o (1-4C)alquilo opcionalmente sustituido con uno o más átomos de fluoro; -Y-(Cn-alquilen)-X- es un grupo enlazante en donde Y está unido a R1 y seleccionado de un enlace, -O-, -CO-, -S-, -SO-, -SO2-, -NH-, -CH>=CH-, -C(CF3)>=CH-, - C≡C-, -CH2-O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, y trans-ciclopropileno; n es un entero de 0 a 10; y X está unido a la unidad estructural fenileno/piridilo y seleccionado de un enlace, -O-, -S-, -SO-,-SO2-, -NH-, - CO-, -CH>=CH-, y trans-ciclopropileno; R2 es H o seleccionados independientemente de uno o más sustituyentes seleccionados de halógeno, (1-4C)alcoxi y (1-4C)alquilo opcionalmente sustituido con uno o más átomos de flúor; y R3 es (1-4C)alquilen-R4 en donde el grupo alquileno puede estar sustituido con uno o más átomos de halógeno o con (CH2)2 para formar una unidad estructural ciclopropilo, o R3 es (3-6C)cicloalquilen-R4, -CH2-(3- 6C)cicloalquilen-R4, (3-6C)cicloalquilen-CH2-R4 o -CO-CH2-R4, en donde R4 es -PO3H2, -OPO3H2, -COOH, - COO(1-4C)alquilo o tetrazol-5-ilo; Q es un enlace; -W-T- se selecciona de -CH>=CH-, -O-CH2-CH2-, -CO-O-, -CH2-CH2-, -CH2-O- y -O-CH2-; R5 es H o independientemente seleccionado de uno o más halógenos; Z es CH, CR2 o N; y A representa una estructura de anillo de morfolina o una amina cíclica de 5, 6 o 7 miembros; o una sal, un solvato o hidrato farmacéuticamente aceptable del mismo o uno o más N-óxidos del mismo

4. 发明专利

CA2804143C SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS 未知
公开(公告)号：CA2804143C
公开(公告)日：2020-03-10
申请号：CA2804143
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： STOIT AXEL , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , VAN DONGEN MARIA J P , LEFLEMME NICOLAS J -L D , HOBSON ADRIAN D
IPC分类号： C07D491/107 , A61K31/438 , A61P25/00 , C07D265/34
摘要： The present invention relates spiro- cyclic amine derivatives of the formula (I) wherein R1; R2; R3; Q; -W-T-; R5; Z; and A have the definitions provided in the claims; 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 (a) S1P receptor (s) is (are) involved.

5. 发明专利

PL2590955T3 Spirocykliczne pochodne aminowe jako modulatory S1P 未知
公开(公告)号：PL2590955T3
公开(公告)日：2017-03-31
申请号：PL11730314
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： STOIT AXEL , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , VAN DONGEN MARIA J P , LEFLEMME NICOLAS J -L D , HOBSON ADRIAN D

6. 发明专利

CA2804137C FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS 未知
公开(公告)号：CA2804137C
公开(公告)日：2019-06-11
申请号：CA2804137
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： SMID PIETER , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , SLIEDREGT LEONARDUS A J M , VAN DONGEN MARIA J P , DEN HARTOG JACOBUS A J , HOBSON ADRIAN D
IPC分类号： C07D487/04 , A61K31/429 , A61K31/4355 , A61K31/4365 , A61K31/437 , A61K31/55 , A61P25/28 , C07D491/04 , C07D498/04 , C07D513/04
摘要： The present invention relates to a fused heterocyclic derivative of the formula (I) The variables R1-R4, z, A, Q, X and Y are as defined in the claims. The following heterocycles are exemplified substructures of formula (I): The compounds of formula (I) are modulators of the S1P receptor (Sphingosine-1-phosphate receptor), More specifically, they are agonists of S1P5. The compounds have therapeutic use in treatment of cognitive disorders, age-relate cognitive decline and dementia.

7. 发明专利

ES2653682T3 Derivados heterocíclicos fusionados como moduladores de S1P 未知
公开(公告)号：ES2653682T3
公开(公告)日：2018-02-08
申请号：ES11733645
申请日：2011-07-08
申请人： ABBVIE BV , ABBVIE INC
发明人： SMID PIETER , IWEMA BAKKER WOUTER , COOLEN HEIN , SLIEDREGT LEONARDUS , VAN DONGEN MARIA , DEN HARTOG JACOBUS , HOBSON ADRIAN D
IPC分类号： C07D471/04 , C07D487/04 , C07D491/04 , C07D491/048 , C07D495/04 , C07D498/04 , C07D513/04
摘要： Un derivado heterocícliclo fusionado de fórmula (I)**Fórmula** donde la fórmula (I) se selecciona entre las fórmulas A, B, C, D y E:**Fórmula** donde R1 se selecciona entre ciano, alquenilo (2-4C), alquinilo (2-4C), alquilo (1-4C), cada uno sustituido opcionalmente con CN o uno o más átomos fluoro, cicloalquilo (3-6C), cicloalquenilo (4-6C) o un grupo bicíclico (8-10C), cada uno sustituido opcionalmente con halógeno o alquilo (1-4C) sustituido opcionalmente con uno o más átomos fluoro, fenilo, bifenilo, naftilo, cada uno sustituido opcionalmente con uno o más sustituyentes seleccionados independientemente entre halógeno, ciano, alquilo (1-4C) sustituido opcionalmente con uno o más átomos fluoro, alcoxi (1-4C) sustituido opcionalmente con uno o más átomos fluoro, amino, dimetilamino y cicloalquilo (3-6C) sustituido opcionalmente con fenilo que puede que esté sustituido con alquilo (1-4C) o halógeno, y fenilo sustituido con fenoxi, bencilo, benciloxi, feniletilo o heterociclo monocíclico, cada uno sustituido opcionalmente con alquilo (1-4C), Z es un grupo conector -W-(Cn-alquileno)-T- donde W está unido a R1 y se selecciona entre un enlace, -O-, -CO-, -S-, -SO-, -SO2-, -NH-, -CH>=CH-, -C(CF3)>=CH-, - C≡C-, -CH2-O-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO- y trans-ciclopropileno; n es un número entero entre 0 y 10; y T está unido al resto fenileno y se selecciona entre un enlace, -O-, -S-, -SO-, -SO2-, -NH-, -CO-, -C>=C-, -C≡C- y trans-ciclopropileno; R2 es H o uno o más sustituyentes seleccionados independientemente entre ciano, halógeno, alquilo (1-4C) sustituido opcionalmente con uno o más átomos halógenos, o alcoxi (1-4C) sustituido opcionalmente con uno o más átomos halógenos; X se selecciona entre C o N; si X es C, R3 se selecciona entre H y alquilo (C1-4), de lo contrario R3 no está presente; Y se selecciona entre NH, O y S; y R4 se selecciona entre -(CH2)2-OH, -CH2-COOH, -(CH2)2-COOH, -(CH2)3-COOH, -CH2-CHCH3-COOH, -CH2- C(CH3)2-COOH, -CHCH3-CH2-COOH, -CH2-CF2-COOH, -CO-CH2-COOH, 1,3-ciclobutileno-COOH, -(CH2)2-PO3H2, -(CH2)3-PO3H2, -(CH2)2-OPO3H2, -(CH2)3-OPO3H2, -CH2-tetrazol-5-ilo, - (CH2)2-tetrazol-5-ilo y -(CH2)3-tetrazol-5-ilo; o un hidrato, un solvato o una sal farmacéuticamente aceptable de este o uno o más N-óxidos de este.

8. 发明专利

AU2015255181A1 SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS 未知
公开(公告)号：AU2015255181A1
公开(公告)日：2015-11-26
申请号：AU2015255181
申请日：2015-11-10
申请人： ABBVIE BV , ABBVIE INC
发明人： STOIT AXEL , IWEMA BAKKER WOUTER I , COOLEN HEIN K A C , VAN DONGEN MARIA J P , LEFLEMME NICOLAS J-L D , HOBSON ADRIAN D
IPC分类号： C07D265/36 , A61K31/407 , A61K31/4355 , A61K31/5386 , A61P25/00 , C07D491/107 , C07D491/20
摘要： Abstract The present invention relates spiro-cyclic amine derivatives of the formula (I) R1 -Y-(Cn-aIkyIene)-X z- A N-R3 W-T R5 (') 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)bicycic 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 monocycic 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 1o-alkylene)-X- is a linking group wherein Y is attached to R1 and selected from a bond, -0-, -CO-, -S-, -SO-, -SO 2 -NH-, -CH=CH-, -C(CF3)=CH-, -C-C-, -CH2-0-, -O-CO-, -CO-0 -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, -CH2-(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH2-R4 or -CO-CH 2-R4, wherein R4 is -OH, PO 3H2 , -OPO3H2 , -COOH, -COO(1-4C)alkyl or tetrazol-5-yl; Q is -0-; -W-T- is selected from -CH=CH-, -CH 2-CH 2-, -CH 2-0-, -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 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 (a) SiP receptor(s) is (are) involved.

9. 发明专利

ZA201300153B SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS 未知
公开(公告)号：ZA201300153B
公开(公告)日：2018-12-19
申请号：ZA201300153
申请日：2013-01-07
申请人： ABBVIE BV
发明人： VAN DONGEN MARIA J P , IWENA BAKKER WOUTER I , LEFLEMME NICOLAS J-LD , COOLEN HEIN K A C , STOIT AXEL , HOBSON ADRIAN D
摘要： 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 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 (a) S1P receptor(s) is (are) involved.

10. 发明专利

ZA201300157B FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS 未知
公开(公告)号：ZA201300157B
公开(公告)日：2017-05-31
申请号：ZA201300157
申请日：2013-01-07
申请人： ABBVIE BV
发明人： DEN HARTOG JACOBUS A J , SLIDREGT LEONARDUS A J M , IWEMA BAKKER WOUTER I , VAN DONGEN MARIA J P , COOLEN HEIN K A C , SMID PIETER , HOBSON ADRIAN D
摘要： The present invention relates to a fused heterocyclic derivative of the formula (I) The variables R1-R4, z, A, Q, X and Y are as defined in the claims. The following heterocycles are exemplified sub-structures of formula (I): The compounds of formula (I) are modulators of the S1P receptor (Sphingosine-1-phosphate receptor), More specifically, they are agonists of S1P5. The compounds have therapeutic use in treatment of cognitive disorders, age-relate cognitive decline and dementia.

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