1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride | 639067-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride
• CAS: 639067-82-6
• 化学式: C₁₇H₂₀ClNO₂
• 分子量: 305.804
• InChiKey: AEHOLYXYGLDBHZ-UHFFFAOYSA-N

物化性质

• 沸点：
  452.3±25.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride 在 氨 作用下， 以 二氯甲烷 为溶剂， 生成 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carboxylic acid amide
  参考文献：
  名称：

  作为 CB1 受体激动剂的吲哚-3-杂环的设计、合成和构效关系

  摘要：

  设计并合成了新型吲哚-3-杂环化合物，并发现其是有效的 CB1 受体激动剂。从微粒体不稳定的铅开始，采用生物等排体方法替代哌嗪酰胺。这被发现是提高体外和体内稳定性的良好策略。结果发现，与先导物相比，它在小鼠甩尾测试中的作用持续时间更长。

  DOI：

  10.1016/j.bmcl.2010.10.093
• 作为产物：
  描述：

  1-(cyclohexylmethyl)-7-methoxyindole-3-carboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 生成 1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride
  参考文献：
  名称：

  作为 CB1 受体激动剂的吲哚-3-杂环的设计、合成和构效关系

  摘要：

  设计并合成了新型吲哚-3-杂环化合物，并发现其是有效的 CB1 受体激动剂。从微粒体不稳定的铅开始，采用生物等排体方法替代哌嗪酰胺。这被发现是提高体外和体内稳定性的良好策略。结果发现，与先导物相比，它在小鼠甩尾测试中的作用持续时间更长。

  DOI：

  10.1016/j.bmcl.2010.10.093

文献信息

• [EN] (INDOL-3-YL)-HETEROCYCLE DERIVATIVES AS AGONISTS OF THE CANNABINOID CB1 RECEPTOR<br/>[FR] DERIVES HETEROCYCLIQUES-(INDOL-3-YL) COMME AGONISTES DU RECEPTEUR DU CANNABINOIDE CB1
  申请人：AKZO NOBEL NV

  公开号：WO2005089754A1

  公开（公告）日：2005-09-29

  The invention relates to (indol-3-yl)-heterocycle derivatives having general Formula (I) wherein A represents a 5-membered aromatic heterocyclic ring, wherein X1, X2 and X3 are independently selected from N, O, S and CR; R is H or (C1-4)alkyl; or R, when present in X2 or X3, may form together with R3 a 5-8 membered ring; R1 is a 5-8 mem­bered saturated carbocyclic ring, optionally containing a heteroatom selected from O and S; R2 is H, CH3 or CH2-CH3; or R2 is joined together with R7 to form a 6-mem­bered ring, optionally containing a heteroatom selected from O and S, and which heteroatom is bonded to the 7-position of the indole ring; R3 and R4 are independent­ly H, (C1-6)alkyl or (C3-7)cycloalkyl, the alkyl groups being optionally substituted with OH, (C1-4)alkyloxy, (C1-4)alkylthio, (C1-4)alkylsulfonyl, CN or halogen; or R3 together with R4 and the N to which they are bonded form a 4-8 membered ring optionally containing a further heteroatom selected from O and S, and which is optionally sub­stituted with OH, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy- (C1-4)alkyl, or halogen; or R3 together with R5 forms a 4-8 membered ring optionally containing a further hetero­atom selected from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy- (C1-4)alkyl, or halogen; or R3 together with R, when present in X2 or X3, forms a 5-8 membered ring; R5 is H or (C1-4)alkyl; or R5 together with R3 forms a 4-8 membered ring optionally containing a further heteroatom select­ed from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyl­oxy, (C1-4) alkyloxy- (C1-4)alkyl, or halogen; R5' is H or (C1-4)alkyl; R6 represents 1-3 substituents independently selected from H, (C1-4 alkyl, (C1-4) alkyloxy, CN and halogen; R7 is H, (C1-4)alkyl, (C1-4)alkyloxy, CN or halogen; or R7 is joined together with R2 to form a 6-membered ring, optionally containing a further heteroatom selected from O and S, and which heteroatom is bonded to the 7-position of the indole ring; or a pharmaceutically acceptable salt thereof, as agonists of the cannabinoid CB1 receptor, which can be used in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.

  该发明涉及具有一般式（I）的（吲哚-3-基）-杂环衍生物，其中A代表一个5-成员芳香杂环环，其中X1、X2和X3分别选自N、O、S和CR；R为H或（C1-4）烷基；或者R，在X2或X3中时，可以与R3一起形成一个5-8成员环；R1是一个5-8成员饱和碳环，可选地含有从O和S中选取的杂原子；R2为H、CH3或CH2- ；或者R2与R7结合形成一个6-成员环，可选地含有从O和S中选取的杂原子，并且该杂原子与吲哚环的7-位置相结合；R3和R4独立地为H、（C1-6）烷基或（C3-7）环烷基，烷基基团可选地用OH、（C1-4）烷氧基、（C1-4）烷基硫醚、（C1-4）烷基磺酰基、CN或卤素取代；或者R3与R4和它们结合的N形成一个4-8成员环，可选地含有从O和S中选取的进一步杂原子，并且可选地用OH、（C1-4）烷基、（C1-4）烷氧基、（C1-4）烷氧基-（C1-4）烷基或卤素取代；或者R3与R5形成一个4-8成员环，可选地含有从O和S中选取的进一步杂原子，并且可选地用OH、（C1-4）烷基、（C1-4）烷氧基、（C1-4）烷氧基-（C1-4）烷基或卤素取代；或者R3与R，在X2或X3中时，形成一个5-8成员环；R5为H或（C1-4）烷基；或者R5与R3一起形成一个4-8成员环，可选地含有从O和S中选取的进一步杂原子，并且可选地用OH、（C1-4）烷基、（C1-4）烷氧基、（C1-4）烷氧基-（C1-4）烷基或卤素取代；R5'为H或（C1-4）烷基；R6代表独立选择的1-3个取代基，选自H、（C1-4）烷基、（C1-4）烷氧基、CN和卤素；R7为H、（C1-4）烷基、（C1-4）烷氧基、CN或卤素；或者R7与R2结合形成一个6-成员环，可选地含有从O和S中选取的进一步杂原子，并且该杂原子与吲哚环的7-位置相结合；或其药学上可接受的盐，作为大麻素CB1受体的激动剂，可用于治疗疼痛，例如围手术期疼痛、慢性疼痛、神经痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛。
• [EN] 1-[(INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES<br/>[FR] DERIVES DE 1-[(INDOL-3-YL)CARBONYL] PIPERAZINE
  申请人：AKZO NOBEL NV

  公开号：WO2004000832A1

  公开（公告）日：2003-12-31

  The present invention relates to 1-[(indol-3-yl)carbonyl]piperazine derivative according to the general formula (I), wherein R represents 1-4 substituents independently selected from H, (C1-4)alkyl (optionally substituted with halogen), (C 1-4)alkyloxy (optionally substituted with halogen), halogen, OH, NH2, CN and NO2; R1 is (C5-8)cycloalkyl or (C5-8)cycloalkenyl; R2 is H, methyl or ethyl; R3, R3', R4' R4', R5, R5' and R6' are independently hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, halogen or OH; R6 is hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, halogen or OH; or R6 forms together with R7 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R7 forms together with R6 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; or R7 is H, (C1-4)alkyl or (C3-5)cycloalkyl, the alkyl groups being optionally substituted with OH, halogen or (C1-4)alkyloxy; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  本发明涉及根据通式（I）的1-[(indol-3-yl)carbonyl]哌嗪衍生物，其中R代表独立选择的1-4个取代基，包括H，（C1-4）烷基（可选择用卤素取代），（C1-4）烷氧基（可选择用卤素取代），卤素，羟基，氨基，氰基和硝基；R1为（C5-8）环烷基或（C5-8）环烯基；R2为H，甲基或乙基；R3，R3'，R4'，R4'，R5，R5'和R6'独立地为氢或（C1-4）烷基，可选择用（C1-4）烷氧基，卤素或羟基取代；R6为氢或（C1-4）烷基，可选择用（C1-4）烷氧基，卤素或羟基取代；或R6与R7一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；R7与R6一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；或R7为H，（C1-4）烷基或（C3-5）环烷基，烷基基团可选择用羟基，卤素或（C1-4）烷氧基取代；或其药学上可接受的盐。该发明还涉及包含所述1-[(indol-3-yl)carbonyl]哌嗪衍生物的药物组合物，并且涉及在治疗疼痛方面使用这些衍生物，如围手术疼痛，慢性疼痛，神经病性疼痛，癌症疼痛以及与多发性硬化症相关的疼痛和痉挛。
• 1-[(Indol-3-yl)carbonyl]piperazine derivatives
  申请人：Cowley Martin Phillip

  公开号：US20050250760A1

  公开（公告）日：2005-11-10

  The present invention relates to 1-[(indol-3-yl)carbonyl]piperazine derivative according to the general formula I or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  本发明涉及一种符合通式I的1-[(indol-3-yl)carbonyl]piperazine衍生物，或其药学上可接受的盐。本发明还涉及包含上述1-[(indol-3-yl)carbonyl]piperazine衍生物的药物组合物，以及利用这些衍生物治疗疼痛，例如围手术期疼痛、慢性疼痛、神经病理性疼痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛。
• 1-[(indol-3-yl)carbonyl]piperazine derivatives
  申请人：N.V. Organon

  公开号：US07304064B2

  公开（公告）日：2007-12-04

  The present invention relates to 1-[(indol-3-yl)carbonyl]piperazine derivative according to the general formula I or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  本发明涉及符合通式I的1-[(indol-3-yl)carbonyl]哌嗪衍生物或其药学上可接受的盐。本发明还涉及包含所述1-[(indol-3-yl)carbonyl]哌嗪衍生物的制药组合物，并且涉及在治疗疼痛，如围手术期疼痛、慢性疼痛、神经病理性疼痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛方面使用这些衍生物。
• 1- (INDOL-3-YL)CARBONYL PIPERAZINE DERIVATIVES
  申请人：N.V. Organon

  公开号：EP1549637B1

  公开（公告）日：2007-05-02