3-[6-(2-,3-dihydro-1,4-benzodioxin-2-ylmethoxy)-2H-spiro [1-benzofuran-3,4'-piperidine]-1'-yl] propanoic acid trifluoroacetic acid | 1355086-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 3-[6-(2-,3-dihydro-1,4-benzodioxin-2-ylmethoxy)-2H-spiro [1-benzofuran-3,4'-piperidine]-1'-yl] propanoic acid trifluoroacetic acid
• 英文别名: 3-[6-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)spiro[2H-1-benzofuran-3,4'-piperidine]-1'-yl]propanoic acid;2,2,2-trifluoroacetic acid
• CAS: 1355086-25-7
• 化学式: C₂HF₃O₂*C₂₄H₂₇NO₆
• 分子量: 539.505
• InChiKey: AUKVHSZEAUGZDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  12

文献信息

• SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS
  申请人：Stoit Axel

  公开号：US20130196998A1

  公开（公告）日：2013-08-01

  The present invention relates to 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 , —COON, —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.

  本发明涉及公式（I）的螺环胺衍生物，其中： R1从氰基，（2-4C）烯基，（2-4C）炔基，（1-4C）烷基中选择，每个基都可以选择性地用CN或一个或多个氟原子取代，（3-6C）环烷基，（4-6C）环烯基或（8-10C）双环基，每个基都可以选择性地用卤素或（1-4C）烷基取代，苯基，联苯基，萘基，每个基都可以选择性地用一个或多个取代基独立选择自卤素，氰基，（1-6C）烷基，可选择性地用一个或多个氟原子取代，（1-6C）烷氧基，可选择性地用一个或多个氟原子取代，氨基，二（1-4C）烷基氨基和（3-6C）环烷基，可选择性地用苯基取代，该苯基可以用（1-4C）烷基或卤素取代，用苯氧基，苄基，苄氧基，苯乙基或单环杂环取代的苯基，每个基都可以选择性地用一个或多个可选择性地用一个或多个氟原子取代的（1-4C）烷基取代，单环杂环可以选择性地独立取代卤素，（1-6C）烷基可选择性地用一个或多个氟原子取代，（3-6C）环烷基或苯基，可选择性地用（1-4C）烷基或卤素取代，和双环杂环，可选择性地用卤素或（1-4C）烷基可选择性地用一个或多个氟原子取代； -Y-（Cn-烷基）-X-是连接基，其中Y连接到R1，并从键，-O-，-CO-，-S-，-SO-，-SO2-，-NH-，-CH═CH-，-C（CF3）═CH-，-C≡C-，-CH2-O-，-O-CO-，-CO-O-，-CO-NH-，-NH-CO-和顺式环丙烷中选择；n是0到10的整数；X连接到苯基/吡啶基团，并从键，-O-，-S-，-SO-，-SO2-，-NH-，-CO-，-CH═CH-和顺式环丙烷中选择；R2是H或从卤素，（1-4C）烷氧基和（1-4C）烷基中独立选择一个或多个取代基，可选择性地用一个或多个氟原子取代；和R3是（1-4C）烷基-R4，其中烷基可以用一个或多个卤素原子或（ ）2取代，以形成环丙基基团，或R3是（3-6C）环烷基-R4，- -（3-6C）环烷基-R4，（3-6C）环烷基- -R4或-CO- -R4，其中R4是-OH，-PO3H2，-OPO3H2，-COON，-COO（1-4C）烷基或四唑-5-基； Q是键或-O-； -W-T-从-CH═CH-，- - -，- -O-，-O- -，-O- - -和-CO-O-中选择； R5是H或从一个或多个卤素中独立选择； Z是CH，CR2或N；和 A表示吗啡啶环结构或5-, 6-或7-环状胺； 或其药学上可接受的盐，溶剂合物或水合物或一个或多个N-氧化物。 本发明的化合物具有对S1P受体的亲和力，并可用于治疗，缓解或预防涉及S1P受体的疾病和情况。
• Spiro-cyclic amine derivatives as S1P modulators
  申请人：Stoit Axel

  公开号：US10179791B2

  公开（公告）日：2019-01-15

  The present invention relates to 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—(Cn-alkylene)-X— is a linking group wherein Y is attached to R1 and selected from a bond, —O—, —CO—, —S—, —SO—, —SO2—, —NH—, —CH═CH—, —C(CF3)═CH—, —C≡C—, —CH2—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—, —SO2—, —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 (CH2)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—CH2—R4, wherein R4 is —OH, —PO3H2, —OPO3H2, —COOH, —COO(1-4C)alkyl or tetrazol-5-yl; Q is a bond or —O—; —W-T- is selected from —CH═CH—, —CH2—CH2—, —CH2—O—, —O—CH2—, —O—CH2—CH2—, 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.

  本发明涉及式 (I) 的螺环胺衍生物 其中 R1 选自 氰基 (2-4C)烯基、(2-4C)炔基、(1-4C)烷基，每个可选被CN或一个或多个氟原子取代、 (3-6C)环烷基、(4-6C)环烯基或(8-10C)双环基团，各自可选被卤素或(1-4C)烷基取代、 苯基、联苯基、萘基，各自任选被一个或多个取代基取代，取代基独立选自卤素、氰基、任选被一个或多个氟原子取代的(1-6C)烷基、任选被一个或多个氟原子取代的(1-6C)烷氧基、氨基、二(1-4C)烷基氨基和任选被苯基取代的(3-6C)环烷基，苯基可被(1-4C)烷基或卤素取代、 被苯氧基、苄基、苄氧基、苯乙基或单环杂环取代的苯基，每个苯基可选 被一个或多个氟原子取代的(1-4C)烷基、 可选地被卤素、可选地被一个或多个氟原子取代的(1-6C)烷基、(3-6C)环烷基或可选地被(1-4C)烷基或卤素取代的苯基取代的单环杂环、 和 任选被卤素或任选被一个或多个氟原子取代的(1-4C)烷基取代的双环杂环； -Y-(Cn-烷基)-X-是连接基团，其中 Y 连接到 R1 并选自键、-O-、-CO-、-S-、-SO-、-SO2-、-NH-、-CH═CH-、-C(CF3)═CH-、-C≡C-、-CH2-O-、-O-CO-、-CO-O-、-CO-NH-、-NH-CO-和反式环丙烯； n 是 0-10 之间的整数；以及 X 连接至苯基/吡啶基，选自键、-O-、-S-、-SO-、-SO2-、-NH-、-CO-、-CH═CH- 和反式环丙烯； R2 是 H 或独立选自卤素、(1-4C)烷氧基和任选被一个或多个氟原子取代的(1-4C)烷基的一个或多个取代基；以及 R3 是(1-4C)亚烷基-R4，其中亚烷基可被一个或多个卤素原子或 ( )2 取代以形成环丙基，或 R3 是(3-6C)环亚烷基-R4、- -(3-6C)环亚烷基-R4、(3-6C)环亚烷基- -R4 或-CO- -R4，其中 R4 是-OH、-PO3H2、-OPO3H2、-COOH、-COO(1-4C)烷基或四唑-5-基； Q 是键或-O-； -W-T-选自-CH═CH-、- - -、- -O-、-O- -、-O- - -和-CO-O-； R5 是 H 或独立选自一种或多种卤素； Z 是 CH、CR2 或 N；以及 A 代表吗啉环结构或 5、6 或 7 元环胺； 或其药学上可接受的盐、溶液或水合物或其一种或多种 N-氧化物。 本发明的化合物对 S1P 受体具有亲和力，可用于治疗、缓解或预防涉及 S1P 受体的疾病和病症。
• US9951084B2
  申请人：——

  公开号：US9951084B2

  公开（公告）日：2018-04-24