7-methoxy-2-oxo-2H-chromene-3-carboxylic acid | 21052-47-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-methoxy-2-oxo-2H-chromene-3-carboxylic acid
• 英文别名: 7-methoxy-2-oxo-2H-chromene-3-carboxylic acid amide；7-Methoxy-cumarin-3-carbonsaeureamid；7-Methoxy-2-oxochromene-3-carboxamide
• CAS: 21052-47-1
• 化学式: C₁₁H₉NO₄
• mdl: MFCD00488541
• 分子量: 219.197
• InChiKey: FFYQZSSICWVFHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-methoxy-2-oxo-2H-chromene-3-carboxylic acid 、 N-(7-aminoheptyl)-1,2,3,4-tetrahydroacridin-9-amine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以51%的产率得到7-methoxy-2-oxo-N-(7-((1,2,3,4-tetrahydroacridin-9-yl)amino)heptyl)-2H-chromene-3-carboxamide
  参考文献：
  名称：

  Syntheses of coumarin–tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase

  摘要：

  Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (Ki=16.7nM) against human AChE and about 2-fold lower potency (Ki=16.1nM) against BChE than tacrine (Ki=35.7nM for AChE, Ki=8.7nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both Aβ aggregation and β-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery.

  DOI：

  10.1016/j.bmc.2014.06.057

文献信息

• Compounds and Methods
  申请人：Baltzer Lars

  公开号：US20130261013A1

  公开（公告）日：2013-10-03

  A molecular tool for use in a method of providing a molecule that is capable of binding a target molecule based on a set of polypeptides. A polypeptide having a sequence selected from SEQ ID NOs 1-32. The polypeptide may be used in a method of screening for a ligand-polypeptide conjugate capable of binding a target molecule for the ligand. A ligand-polypeptide conjugate, useful e.g. in therapy.

  一种分子工具，可用于提供一种能够基于一组多肽结合目标分子的分子。其中一种多肽具有从SEQ ID NOs 1-32中选择的序列。该多肽可用于筛选配体-多肽共轭物，以便为配体结合目标分子。配体-多肽共轭物可用于治疗等方面。
• COMPOUNDS AND METHODS
  申请人：Modpro AB

  公开号：EP2613796A2

  公开（公告）日：2013-07-17
• US9377466B2
  申请人：——

  公开号：US9377466B2

  公开（公告）日：2016-06-28
• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET PROCÉDÉS
  申请人：MODPRO AB

  公开号：WO2012032068A2

  公开（公告）日：2012-03-15

  A molecular tool for use in a method of providing a molecule that is capable of binding a target molecule based on a set of polypeptides. A polypeptide having a sequence selected from SEQ ID NOs 1-32. The polypeptide may be used in a method of screening for a ligand- polypeptide conjugate capable of binding a target molecule for the ligand. A ligand- polypeptide conjugate, useful e.g. in therapy.
• Syntheses of coumarin–tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase
  作者：Qi Sun、Da-Yong Peng、Sheng-Gang Yang、Xiao-Lei Zhu、Wen-Chao Yang、Guang-Fu Yang

  DOI：10.1016/j.bmc.2014.06.057

  日期：2014.9

  Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (Ki=16.7nM) against human AChE and about 2-fold lower potency (Ki=16.1nM) against BChE than tacrine (Ki=35.7nM for AChE, Ki=8.7nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both Aβ aggregation and β-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery.