(-)-furan-2-yl-((3aR,4S,7aR)-4-hydroxy-4-(m-tolylethynyl)-octahydro-indol-1-yl)-methanone | 543906-20-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (-)-furan-2-yl-((3aR,4S,7aR)-4-hydroxy-4-(m-tolylethynyl)-octahydro-indol-1-yl)-methanone
• 英文别名: (-)-(3aR,4S,7aR)-furan-2-yl-(4-hydroxy-4-(m-tolylethynyl)octahydroindol-1-yl)methanone；(-)-(3aR,4S,7aR)-furan-2-yl-(4-hydroxy-4-m-tolylethynyl-octahydro-indol-1-yl)-methanone；[(3aR,4S,7aR)-4-hydroxy-4-[2-(3-methylphenyl)ethynyl]-3,3a,5,6,7,7a-hexahydro-2H-indol-1-yl]-(furan-2-yl)methanone
• CAS: 543906-20-3
• 化学式: C₂₂H₂₃NO₃
• 分子量: 349.43
• InChiKey: NMIXTTBVZMBIHL-WOIUINJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  53.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,5,6,7-四氢-4H-吲哚-4-酮 在 盐酸 、 正丁基锂 、 草酰氯 、 platinum on carbon 、 potassium tert-butylate 、 氢气 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 为溶剂， -60.0~20.0 ℃ 、100.0 kPa 条件下， 反应 106.67h， 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

文献信息

• ACETYLENE DERIVATIVES HAVING MGLUR 5 ANTAGONISTIC ACTIVITY
  申请人：Gasparini Fabrizio

  公开号：US20130331568A1

  公开（公告）日：2013-12-12

  The invention provides compounds of formula I wherein 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.

  本发明提供了公式I的化合物，其中n，A，R，R′，R″，R0，X和Y的定义如描述中所定义，并提供其制备方法。公式I的化合物可用作药物。
• 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。
• USES OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Ralf Glatthar

  公开号：US20100041641A1

  公开（公告）日：2010-02-18

  The invention concerns the use an mGluR modulator, e.g. an mGluR5 modulator, for the treatment, prevention or delay of progression of cognitive dysfunction.

  本发明涉及使用mGluR调节剂，例如mGluR5调节剂，用于治疗、预防或延缓认知功能障碍的进展。
• USE OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：GLATTHAR Ralf

  公开号：US20120309742A1

  公开（公告）日：2012-12-06

  The invention concerns the use an mGluR modulator, e.g. an mGluR5 modulator, for the treatment, prevention or delay of progression of cognitive dysfunction.

  本发明涉及使用mGluR调节剂，例如mGluR5调节剂，用于治疗、预防或延缓认知功能障碍的进展。
• New Uses of metabotropic glutamate receptors
  申请人：Novartis AG

  公开号：EP2272509A1

  公开（公告）日：2011-01-12

  The invention concerns the use an mGluR modulator, e.g. an mGluR5 modulator, for the treatment, prevention or delay of progression of cognitive dysfunction.

  本发明涉及使用 mGluR 调节剂（如 mGluR5 调节剂）治疗、预防或延缓认知功能障碍的进展。