3-{2-[4-(2-fluoro-6-trifluoromethyl-phenoxy)-phenyl]-morpholin-4-yl}-propionic acid hydrochloride | 1354304-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 3-{2-[4-(2-fluoro-6-trifluoromethyl-phenoxy)-phenyl]-morpholin-4-yl}-propionic acid hydrochloride
• 英文别名: 3-[2-[4-[2-Fluoro-6-(trifluoromethyl)phenoxy]phenyl]morpholin-4-yl]propanoic acid;hydrochloride
• CAS: 1354304-82-7
• 化学式: C₂₀H₁₉F₄NO₄*ClH
• 分子量: 449.83
• InChiKey: IRKJHIQTGDUTGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.91
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59
• 氢给体数：
  2
• 氢受体数：
  9

文献信息

• [EN] BISARYL (THIO)MORPHOLINE DERIVATIVES AS S1P MODULATORS<br/>[FR] DÉRIVÉS BISARYL (THIO)MORPHOLINES MODULATEURS DE S1P
  申请人：ABBOTT HEALTHCARE PRODUCTS BV

  公开号：WO2012004375A1

  公开（公告）日：2012-01-12

  The present invention relates to bisaryl (thio)morpholine derivatives of the formula (I) wherein R1 is an aryl substitutent selected from phenyl, pyridyl, pyrimidinyl, biphenyl and naphthyl, each optionally substituted with one or more substituents independently selected from halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino, -SO2-(1-4C)alkyl, -CO-(1-4C)alkyl, -CO-O-(1-4C)alkyl and -NH-CO-(1-4C)alkyl, or substituted with phenoxy, benzyl, benzyloxy, phenylethyl or morpholinyl, each optionally substituted with (1-4C)alkyl, and (8-10C)bicyclic group, bicyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms or oxo; A is selected from -CO-, -NH-, -O-, -S-, -SO- or -SO2-; ring structure B optionally contains one nitrogen atom; R2 is H, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, or halogen; and R3 is (1-4C)alkylene-R6 wherein the alkylene group may be substituted with (CH2)2 to form a cyclopropyl moiety or with one or more halogen atoms, or R3 is (3-6C)cycloalkylene-R5 or -CO-CH2-R6, wherein R6 is -OH, -PO3H2, -OPO3H2, -COOH, -COO(1-4C)alkyl or tetrazol-5-yl; R4 is H or (1-4C)alkyl; R5 is one or more substituents independently selected from H, (1-4C)alkyl or oxo; W is -O-, -S-, -SO- or -SO2-; or a pharmaceutically acceptable salt, a solvate or hydrate thereof, with the proviso that the derivative of formula (I) is not 2-[4-(4-chlorophenoxy)-2-chloro-phenyl]-4-morpholineethanol. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of S1P receptor mediated diseases and conditions.

  本发明涉及公式（I）的双芳基（硫）吗啡啉衍生物，其中R1是从苯基、吡啶基、嘧啶基、联苯基和萘基中选择的芳基取代基，每个基可选择地取代一个或多个从卤素、（1-6C）烷基（可选择地取代一个或多个氟原子）、（1-4C）氧烷基（可选择地取代一个或多个氟原子）、氨基、二（1-4C）烷基氨基、-SO2-（1-4C）烷基、-CO-（1-4C）烷基、-CO-O-（1-4C）烷基和-NH-CO-（1-4C）烷基中独立选择的取代基，或取代有苯氧基、苄基、苄氧基、苯乙基或吗啡啉基的基，每个基可选择地取代（1-4C）烷基和（8-10C）双环基团、双环杂环基，每个基可选择地取代一个或多个氟原子或氧代基；A从-CO-、-NH-、-O-、-S-、-SO-或-SO2-中选择；环结构B可选择地含有一个氮原子；R2是H、（1-4C）烷基（可选择地取代一个或多个氟原子）、（1-4C）氧烷基（可选择地取代一个或多个氟原子）或卤素；R3是（1-4C）烷基烯基-R6，其中烷基烯基可被（CH2）2取代以形成环丙基基团或取代一个或多个卤素原子，或R3是（3-6C）环烷基烯基-R5或-CO- -R6，其中R6是-OH、-PO3H2、-OPO3H2、-COOH、-COO（1-4C）烷基或四唑-5-基；R4是H或（1-4C）烷基；R5是从H、（1-4C）烷基或氧代基中独立选择的一个或多个取代基；W是-O-、-S-、-SO-或-SO2-；或其药学上可接受的盐、溶剂或水合物，但公式（I）的衍生物不是2-[4-(4-氯苯氧基)-2-氯苯基]-4-吗啡啉乙醇。本发明的化合物具有对S1P受体的亲和力，可用于治疗、缓解或预防S1P受体介导的疾病和症状。
• BISARYL (THIO)MORPHOLINE DERIVATIVES AS S1P MODULATORS
  申请人：Iwema Bakker Wouter I.

  公开号：US20130203745A1

  公开（公告）日：2013-08-08

  The present invention relates to bisaryl(thio)morpholine derivatives of the formula (I) wherein R1 is an aryl substitutent selected from phenyl, pyridyl, pyrimidinyl, biphenyl and naphthyl, each optionally substituted with one or more substituents independently selected from halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino, —SO 2 -(1-4C)alkyl, —CO-(1-4C)alkyl, —CO—O-(1-4C)alkyl and —NH—CO-(1-4C)alkyl, or substituted with phenoxy, benzyl, benzyloxy, phenylethyl or morpholinyl, each optionally substituted with (1-4C)alkyl, and (8-10C)bicyclic group, bicyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms or oxo; A is selected from —CO—, —NH—, —O—, —S—, —SO— or —SO 2 —; ring structure B optionally contains one nitrogen atom; R2 is H, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, or halogen; and R3 is (1-4C)alkylene-R6 wherein the alkylene group may be substituted with (CH 2 ) 2 to form a cyclopropyl moiety or with one or more halogen atoms, or R3 is (3-6C)cycloalkylene-R5 or —CO—CH 2 —R6, wherein R6 is —OH, —PO 3 H 2 , —OPO 3 H 2 , —COOH, —COO(1-4C)alkyl or tetrazol-5-yl; R4 is H or (1-4C)alkyl; R5 is one or more substituents independently selected from H, (1-4C)alkyl or oxo; W is —O—, —S—, —SO— or —SO 2 —; or a pharmaceutically acceptable salt, a solvate or hydrate thereof, with the proviso that the derivative of formula (I) is not 2-[4-(4-chlorophenoxy)-2-chloro-phenyl]-4-morpholineethanol. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of S1P receptor mediated diseases and conditions.

  本发明涉及公式（I）的双芳基（硫）吗啡啶衍生物， 其中， R1是苯基，吡啶基，嘧啶基，联苯基和萘基中选择的芳基取代基，每个取代基可以独立地选择卤素，（1-6C）烷基，可选地取代一个或多个氟原子，（1-4C）烷氧基，可选地取代一个或多个氟原子，氨基，二（1-4C）烷基氨基，—SO2-（1-4C）烷基，—CO-（1-4C）烷基，—CO—O-（1-4C）烷基和—NH—CO-（1-4C）烷基，或用苯氧基，苄基，苄氧基，苯乙基或吗啡啶基取代，每个取代基可以独立地选择（1-4C）烷基和（8-10C）双环基，双环杂环，每个取代基可以独立地选择（1-4C）烷基，可选地取代一个或多个氟原子或氧代； A选择自—CO—，—NH—，—O—，—S—，—SO—或—SO2—； 环结构B可选地含有一个氮原子； R2为H，（1-4C）烷基，可选地取代一个或多个氟原子的（1-4C）烷氧基或卤素； R3为（1-4C）烷基-R6，其中烷基可以用（CH2）2取代以形成环丙基基团或用一个或多个卤素原子取代，或者R3为（3-6C）环烷基-R5或—CO— —R6，其中R6为—OH，—PO3H2，—OPO3H2，—COOH，—COO（1-4C）烷基或四唑-5-基； R4为H或（1-4C）烷基； R5为一个或多个取代基，可以独立地选择H，（1-4C）烷基或氧代； W为—O—，—S—，—SO—或—SO2—； 或其药学上可接受的盐、溶剂化合物或水合物，但公式（I）的衍生物不是2-[4-(4-氯苯氧基)-2-氯苯基]-4-吗啡啶乙醇。本发明的化合物具有亲和力S1P受体，可用于治疗、缓解或预防S1P受体介导的疾病和病情。
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  公开号：US9029371B2

  公开（公告）日：2015-05-12
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