(3aR,4S,7aR)-八氢-4-羟基-1H-吲哚-1-羧酸1,1-二甲基乙基酯 | 543910-49-2

• 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
• 中文名称: (3aR,4S,7aR)-八氢-4-羟基-1H-吲哚-1-羧酸1,1-二甲基乙基酯
• 中文别名: (3aR,7aR)-八氢-4-羟基-1H-吲哚-1-羧酸叔丁酯
• 英文名称: (3aRS,4SR,7aRS)-4-hydroxy-octahydro-indole-1-carboxylic acid tert-butyl ester
• 英文别名: tert-Butyl (3aR,4S,7aR)-4-hydroxyoctahydro-1H-indole-1-carboxylate；tert-butyl (3aR,4S,7aR)-4-hydroxy-2,3,3a,4,5,6,7,7a-octahydroindole-1-carboxylate
• CAS: 543910-49-2
• 化学式: C₁₃H₂₃NO₃
• 分子量: 241.331
• InChiKey: MRMYRYLVMIZVQM-MXWKQRLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (3aR,4S,7aR)-八氢-4-羟基-1H-吲哚-1-羧酸1,1-二甲基乙基酯 在 盐酸 、 正丁基锂 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 12.67h， 生成 (-)-furan-2-yl-((3aR,4S,7aR)-4-hydroxy-4-(m-tolylethynyl)-octahydro-indol-1-yl)-methanone
  参考文献：
  名称：

  AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: Identification, SAR and pharmacological characterization

  摘要：

  Here we describe the identification, structure-activity relationship and the initial pharmacological characterization of AFQ056/mavoglurant, a structurally novel, non-competitive mGlu5 receptor antagonist. AFQ056/mavoglurant was identified by chemical derivatization of a lead compound discovered in a HTS campaign. In vitro, AFQ056/mavoglurant had an IC50 of 30 nM in a functional assay with human mGluR5 and was selective over the other mGluR subtypes, iGluRs and a panel of 238 CNS relevant receptors, transporter or enzymes. In vivo, AFQ056/mavoglurant showed an improved pharmacokinetic profile in rat and efficacy in the stress-induced hyperthermia test in mice as compared to the prototypic mGluR5 antagonist MPEP. The efficacy of AFQ056/mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.09.033
• 作为产物：
  描述：

  1,5,6,7-四氢-4H-吲哚-4-酮 在 platinum on carbon 、 potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 94.0h， 生成 (3aR,4S,7aR)-八氢-4-羟基-1H-吲哚-1-羧酸1,1-二甲基乙基酯
  参考文献：
  名称：

  AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: Identification, SAR and pharmacological characterization

  摘要：

  Here we describe the identification, structure-activity relationship and the initial pharmacological characterization of AFQ056/mavoglurant, a structurally novel, non-competitive mGlu5 receptor antagonist. AFQ056/mavoglurant was identified by chemical derivatization of a lead compound discovered in a HTS campaign. In vitro, AFQ056/mavoglurant had an IC50 of 30 nM in a functional assay with human mGluR5 and was selective over the other mGluR subtypes, iGluRs and a panel of 238 CNS relevant receptors, transporter or enzymes. In vivo, AFQ056/mavoglurant showed an improved pharmacokinetic profile in rat and efficacy in the stress-induced hyperthermia test in mice as compared to the prototypic mGluR5 antagonist MPEP. The efficacy of AFQ056/mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.09.033

文献信息

• [EN] ACETYLENE DERIVATIVES HAVING MGLUR 5 ANTAGONISTIC ACTIVITY<br/>[FR] DERIVES D'ACETYLENE POSSEDANT UNE ACTIVITE ANTAGONISTE MGLUR 5
  申请人：NOVARTIS AG

  公开号：WO2003047581A1

  公开（公告）日：2003-06-12

  The invention provides compounds of formula (I) wherein m, n, A, R, R', R', Ro, X and Y are as defined in the description, and their preparation. The compounds of formula (I) are useful as pharmaceuticals in the treatment of e.g. nervous system disorders.

  该发明提供了式（I）的化合物，其中m，n，A，R，R'，R''，Ro，X和Y如描述中所定义，并提供其制备方法。式（I）的化合物在治疗神经系统疾病等方面作为药物是有用的。
• Acetylene derivatives having mglur 5 antagonistic activity
  申请人：Gasparini Fabrizio

  公开号：US20050065191A1

  公开（公告）日：2005-03-24

  The invention provides compounds of formula (I) wherein m, n, A, R, R′, R″, R 0 , X and Y are as defined in the description, and their preparation. The compounds of formula (I) are useful as pharmaceuticals in the treatment of e.g. nervous system disorders.

  本发明提供了式(I)的化合物，其中m、n、A、R、R'、R''、R0、X和Y如描述中所定义，并提供了它们的制备方法。式(I)的化合物可用于治疗例如神经系统疾病等药物。
• ACETYLENE DERIVATIVES HAVING MGLUR 5 ANTAGONISTIC ACTIVITY
  申请人：Gasparini Fabrizio

  公开号：US20080146647A1

  公开（公告）日：2008-06-19

  The invention provides compounds of formula I wherein n, A, R, R′, R″, R o , X and Y are as defined in the description, and their preparation. The compounds of formula I are useful as pharmaceuticals.

  本发明提供了I式化合物，其中n、A、R、R'、R"、Ro、X和Y如描述中所定义，并提供它们的制备方法。I式化合物可用作药物。
• US7348353B2
  申请人：——

  公开号：US7348353B2

  公开（公告）日：2008-03-25
• US8536229B2
  申请人：——

  公开号：US8536229B2

  公开（公告）日：2013-09-17