(1S,2S)-2-(3-fluorophenyl)-N-[(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]cyclopropane-1-carboxamide | 1531592-42-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (1S,2S)-2-(3-fluorophenyl)-N-[(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]cyclopropane-1-carboxamide
• CAS: 1531592-42-3
• 化学式: C₁₉H₂₀FNO₃
• 分子量: 329.371
• InChiKey: MKOFAEMSCPVRRX-SQNIBIBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴苯甲醚 在 盐酸 、 甲基叔丁基醚 、 叔丁基锂 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (1S,2S)-2-(3-fluorophenyl)-N-[(1R)-2-hydroxy-1-(4-methoxyphenyl)ethyl]cyclopropane-1-carboxamide
  参考文献：
  名称：

  Discovery and optimization of Lu AF58801, a novel, selective and brain penetrant positive allosteric modulator of alpha-7 nicotinic acetylcholine receptors: Attenuation of subchronic phencyclidine (PCP)-induced cognitive deficits in rats following oral administration

  摘要：

  In this Letter, we describe a chemical lead optimization campaign starting from a novel, weak alpha 7 nicotinic acetylcholine receptor positive allosteric modulator (PAM) hit from a HTS screen. Exploration of the structure-activity relationships for alpha 7 PAM potency, intrinsic hepatic clearance, the structure-property relationships for lipophilicity, and thermodynamic solubility, led to the identification of Lu AF58801: a potent, orally available, brain penetrant PAM of the alpha 7 nicotinic acetylcholine receptor, showing efficacy in a novel object recognition task in rats treated subchronically with phencyclidine (PCP). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.022

文献信息

• New positive allosteric modulators of nicotinic acetylcholine receptor
  申请人：H. LUNDBECK A/S

  公开号：US20150315130A1

  公开（公告）日：2015-11-05

  The present invention relates to compounds useful in therapy, to compositions comprising said compounds, and to methods of treating diseases comprising administration of said compounds. The compounds referred to are positive allosteric modulators (PAMs) of the nicotinic acetylcholine α7 receptor.

  本发明涉及在治疗中有用的化合物，包括含有该化合物的组合物，以及通过给予该化合物治疗疾病的方法。所提到的化合物是尼古丁乙酰胆碱α7受体的正向变构调节剂（PAMs）。
• [EN] NEW POSITIVE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTOR<br/>[FR] NOUVEAUX MODULATEURS ALLOSTÉRIQUES POSITIFS D'UN RÉCEPTEUR NICOTINIQUE DE L'ACÉTYLCHOLINE
  申请人：LUNDBECK & CO AS H

  公开号：WO2014090731A1

  公开（公告）日：2014-06-19

  The present invention relates to compounds useful in therapy, to compositions comprising said compounds, and to methods of treating diseases comprising administration of said compounds. The compounds referred to are positive allosteric modulators (PAMs) of the nicotinic acetylcholine α7 receptor.
• Discovery and optimization of Lu AF58801, a novel, selective and brain penetrant positive allosteric modulator of alpha-7 nicotinic acetylcholine receptors: Attenuation of subchronic phencyclidine (PCP)-induced cognitive deficits in rats following oral administration
  作者：Jørgen Eskildsen、John P. Redrobe、Anette G. Sams、Kim Dekermendjian、Morten Laursen、Jette B. Boll、Roger L. Papke、Christoffer Bundgaard、Kristen Frederiksen、Jesper F. Bastlund

  DOI：10.1016/j.bmcl.2013.11.022

  日期：2014.1

  In this Letter, we describe a chemical lead optimization campaign starting from a novel, weak alpha 7 nicotinic acetylcholine receptor positive allosteric modulator (PAM) hit from a HTS screen. Exploration of the structure-activity relationships for alpha 7 PAM potency, intrinsic hepatic clearance, the structure-property relationships for lipophilicity, and thermodynamic solubility, led to the identification of Lu AF58801: a potent, orally available, brain penetrant PAM of the alpha 7 nicotinic acetylcholine receptor, showing efficacy in a novel object recognition task in rats treated subchronically with phencyclidine (PCP). (C) 2013 Elsevier Ltd. All rights reserved.