1-(3,5-Difluorophenyl)-3-[4-methoxy-3-(2-piperidin-1-ylethoxy)phenyl]imidazol-2-one | 561277-52-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3,5-Difluorophenyl)-3-[4-methoxy-3-(2-piperidin-1-ylethoxy)phenyl]imidazol-2-one
• CAS: 561277-52-9
• 化学式: C₂₃H₂₅F₂N₃O₃
• 分子量: 429.467
• InChiKey: MEFXMBYDODZESE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  45.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3,5-Difluorophenyl)-3-[4-methoxy-3-(2-piperidin-1-ylethoxy)phenyl]imidazol-2-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 1-(3,5-Difluorophenyl)-3-[4-methoxy-3-(2-piperidin-1-ylethoxy)phenyl]imidazolidin-2-one
  参考文献：
  名称：

  A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists

  摘要：

  Bisaryl cyclic ureas have been identified as high affinity 5-HT2C receptor antagonists with selectivity over 5-HT2A and 5-HT2B. Compounds such as 8 and 22 have shown oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function in rodents. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.004
• 作为产物：
  描述：

  2-甲氧基-5-硝基苯酚 在 palladium on activated charcoal 盐酸 、 氢气 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 92.0h， 生成 1-(3,5-Difluorophenyl)-3-[4-methoxy-3-(2-piperidin-1-ylethoxy)phenyl]imidazol-2-one
  参考文献：
  名称：

  A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists

  摘要：

  Bisaryl cyclic ureas have been identified as high affinity 5-HT2C receptor antagonists with selectivity over 5-HT2A and 5-HT2B. Compounds such as 8 and 22 have shown oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function in rodents. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.004

文献信息

• [EN] CYCLIC UREA DERIVATIVES WITH 5-HT2C RECEPTOR ACTIVITY<br/>[FR] DERIVES CYCLIQUES D'UREE POSSEDANT UNE ACTIVITE DE RECEPTEURS 5-HT2C
  申请人：GLAXO GROUP LTD

  公开号：WO2003057220A1

  公开（公告）日：2003-07-17

  Compounds of formula (I) or a pharmaceutically acceptable salt thereof, having 5HT2C receptor activity, are disclosed: wherein a is 0, 1, 2, 3, 4 or 5; b is 1, 2 or 3; Y is nitrogen or carbon; A is oxygen, nitrogen, -CONH-, -NHCO- or together with R2 form a benzoxazolone group; R1 is halogen, C¿1-6?alkyl, C1-6alkoxy, C1-6alkylthio, hydroxy, amino, mono- or di-C1-6alkylamino, nitro, CN, CF3, OCF3, aryl, arylC1-6alkyl, arylC1-6alkyloxy or arylC1-6alkylthio; R?2¿ is hydrogen, halogen, C¿1-6?alkyl, C1-6alkoxy, haloC1-6alkyl or haloC1-6alkoxy; R?3¿ is: (i) -NR4R5 where R?4 and R5¿ are independently hydrogen, C¿1-6?alkyl or arylC1-6alkyl; or (ii) an optionally substituted N-linked heterocycle; or (iii) an optionally substituted C-linked heterocycle; ======= is a single bond or a double bond; and X is CH2 or C = O (when ======= is a single bond) or X is CH (when ======= is a double bond). The preparation of these compounds and their use in therapy, especially for a CNS disorder such as depression or anxiety, are also disclosed.

  公开了式（I）的化合物或其药学上可接受的盐，具有5HT2C受体活性：其中a为0、1、2、3、4或5；b为1、2或3；Y为氮或碳；A为氧、氮、-CONH-、-NHCO-或与R2一起形成苯并噁唑酮基团；R1为卤素、C1-6烷基、C1-6烷氧基、C1-6烷基硫基、羟基、氨基、单基或双C1-6烷基氨基、硝基、CN、CF3、OCF3、芳基、芳基C1-6烷基、芳基C1-6烷氧基或芳基C1-6烷硫基；R2为氢、卤素、C1-6烷基、C1-6烷氧基、卤代C1-6烷基或卤代C1-6烷氧基；R3为：（i）-NR4R5，其中R4和R5独立地为氢、C1-6烷基或芳基C1-6烷基；或（ii）可选地取代的N-连接杂环；或（iii）可选地取代的C-连接杂环；=======为单键或双键；X为CH2或C = O（当=======为单键时）或X为CH（当=======为双键时）。还公开了这些化合物的制备及其在治疗中的用途，特别是用于中枢神经系统疾病，如抑郁症或焦虑症。
• Cyclic urea derivatives with 5-ht2c receptor activity
  申请人：Bromidge M Steven

  公开号：US20050154028A1

  公开（公告）日：2005-07-14

  Compounds of formula (I) or a pharmaceutically acceptable salt thereof, having 5HT 2C receptor activity, are disclosed: wherein a is 0,1,2,3,4 or 5; b is 1,2 or 3; Y is nitrogen or carbon; A is oxygen, nitrogen, —CONH—, —NHCO— or together with R 2 form a benzoxazolone group; R 1 is halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy, amino, mono- or di-C 1-6 alkylamino, nitro, CN, CF 3 , OCF 3 , aryl, arylC 1-6 alkyl, arylC 1-6 alkyloxy or arylC 1-6 alkylthio; R 2 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkyl or haloC 1-6 alkoxy; R 3 is: (i) —NR 4 R 5 where R 4 and R 5 are independently hydrogen, C 1-6 alkyl or arylC 1-6 alkyl; or (ii) an optionally substituted N-linked heterocycle; or (iii) an optionally substituted C-linked heterocycle; ======= is a single bond or a double bond; and X is CH 2 or C═O (when ======= is a single bond) or X is CH (when ======= is a double bond). The preparation of these compounds and their use in therapy, especially for a CNS disorder such as depression or anxiety, are also disclosed.

  公开了式(I)化合物或其药学上可接受的盐，具有5HT2C受体活性：其中a为0、1、2、3、4或5；b为1、2或3；Y为氮或碳；A为氧、氮、-CONH-、-NHCO-或与R2一起形成苯并噁唑酮基团；R1为卤素、C1-6烷基、C1-6烷氧基、C1-6烷基硫基、羟基、氨基、单-或双C1-6烷基氨基、硝基、CN、CF3、OCF3、芳基、芳基C1-6烷基、芳基C1-6烷氧基或芳基C1-6烷硫基；R2为氢、卤素、C1-6烷基、C1-6烷氧基、卤代C1-6烷基或卤代C1-6烷氧基；R3为：（i）-NR4R5，其中R4和R5独立地为氢、C1-6烷基或芳基C1-6烷基；或（ii）可选地取代的N-连接杂环；或（iii）可选地取代的C-连接杂环；=======为单键或双键；X为CH2或C═O（当=======为单键时）或X为CH（当=======为双键时）。还公开了这些化合物的制备及其在治疗中的使用，特别是用于中枢神经系统障碍，如抑郁症或焦虑症。
• CYCLIC UREA DERIVATIVES WITH 5-HT2C RECEPTOR ACTIVITY
  申请人：GLAXO GROUP LIMITED

  公开号：EP1465630A1

  公开（公告）日：2004-10-13
• A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists
  作者：Caroline J. Goodacre、Steven M. Bromidge、David Clapham、Frank D. King、Peter J. Lovell、Mike Allen、Lorraine P. Campbell、Vicky Holland、Graham J. Riley、Kathryn R. Starr、Brenda K. Trail、Martyn D. Wood

  DOI：10.1016/j.bmcl.2005.08.004

  日期：2005.11

  Bisaryl cyclic ureas have been identified as high affinity 5-HT2C receptor antagonists with selectivity over 5-HT2A and 5-HT2B. Compounds such as 8 and 22 have shown oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function in rodents. (c) 2005 Elsevier Ltd. All rights reserved.