(S,S)-1-carbethoxy-4-ketoperhydroindole | 1207628-35-0

• 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: (S,S)-1-carbethoxy-4-ketoperhydroindole
• 英文别名: Ethyl (3aS,7aS)-4-oxooctahydro-1H-indole-1-carboxylate；ethyl (3aS,7aS)-4-oxo-3,3a,5,6,7,7a-hexahydro-2H-indole-1-carboxylate
• CAS: 1207628-35-0
• 化学式: C₁₁H₁₇NO₃
• 分子量: 211.261
• InChiKey: QDRBYOAEDABTEF-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S,S)-1-carbethoxy-4-ketoperhydroindole 在 正丁基锂 、 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 6.75h， 生成 (±)-(3aR,4R,7aR)-4-hydroxy-4-phenethyl-octahydro-indole-1-carboxylic acid methyl ester
  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

• Cholesterol ester-reducing amides of hexahydroindolinols
  申请人：Sandoz, Inc.

  公开号：US04194002A1

  公开（公告）日：1980-03-18

  Long chain fatty acid amides of styryl hexahydroindolinols in which the amido portions have ethyleneically unsaturated positions or cyclopropanyl rings, eg 1-(1-oxo-9-cis-octadecenyl)-(3aRS, 4RS, 7aRS)-4-(Z)-(3,4-dimethoxy)-styryl-hexahydro-4-indolinol, are useful as cholesterol ester-reducing agents and are obtainable by reacting corresponding long chain carboxylic acids (or derivatives thereof) with appropriate 4-styryl-4-hexahydroindolinols.

  长链脂肪酸酰胺的苯乙烯基六氢吲哚醇，其中酰胺部分具有乙烯基不饱和位置或环丙烷基环，例如1-(1-氧代-9-cis-十八碳烯基)-(3aRS，4RS，7aRS)-4-(Z)-(3,4-二甲氧基)-苯乙烯基六氢-4-吲哚醇，可用作胆固醇酯还原剂，并可通过将相应的长链羧酸（或其衍生物）与适当的4-苯乙烯基-4-六氢吲哚醇反应而获得。
• PROCESSES FOR THE PREPARATION OF 4-OXO-OCTAHYDRO-INDOLE-1-CARBOCYCLIC ACID METHYL ESTER AND DERIVATIVES THEREOF
  申请人：Kuesters Ernst

  公开号：US20110144352A1

  公开（公告）日：2011-06-16

  The present invention relates to a process for the production of carbamic acid (2-chloroethyl)(3-oxocyclohexyl)-alkyl ester enantiomers and of 1-carbalkoxy-4-ketoperhydroindole enantiomers.
• US8084487B2
  申请人：——

  公开号：US8084487B2

  公开（公告）日：2011-12-27
• AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: Identification, SAR and pharmacological characterization
  作者：Ivo Vranesic、Silvio Ofner、Peter Josef Flor、Graeme Bilbe、Rochdi Bouhelal、Albert Enz、Sandrine Desrayaud、Kevin McAllister、Rainer Kuhn、Fabrizio Gasparini

  DOI：10.1016/j.bmc.2014.09.033

  日期：2014.11

  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.