6-chloro-2-hydroxy-9H-xanthen-9-one | 37884-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-chloro-2-hydroxy-9H-xanthen-9-one
• 英文别名: 6-chloro-2-hydroxyxanthone；6-chloro-2-hydroxy-xanthen-9-one；6-chloro-2-hydroxyxanthen-9-one
• CAS: 37884-04-1
• 化学式: C₁₃H₇ClO₃
• 分子量: 246.65
• InChiKey: MDAJUFDMGJKYKY-UHFFFAOYSA-N

物化性质

• 沸点：
  450.5±45.0 °C(Predicted)
• 密度：
  1.504±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-2-hydroxy-9H-xanthen-9-one 在 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 生成 6-chloro-2-(5-(4-methylpiperidin-1-yl)pentyloxy)-9H-xanthen-9-one
  参考文献：
  名称：

  Rational design of new multitarget histamine H3 receptor ligands as potential candidates for treatment of Alzheimer’s disease

  摘要：

  Design and development of multitarget-directed ligands (MTDLs) has become a very important approach in the search of new therapies for Alzheimer's disease (AD). In our present research, a number of xanthone derivatives were first designed using a pharmacophore model for histamine H₃ receptor (H₃R) antagonists/inverse agonists, and virtual docking was then performed for the enzyme acetylcholinesterase. Next, 23 compounds were synthesised and evaluated in vitro for human H₃R (hH₃R) affinity and inhibitory activity on cholinesterases. Most of the target compounds showed hH₃R affinities in nanomolar range and exhibited cholinesterase inhibitory activity with IC₅₀ values in submicromolar range. Furthermore, the inhibitory effects of monoamine oxidases (MAO) A and B were investigated. The results showed low micromolar and selective human MAO B (hMAO B) inhibition. Two azepane derivatives, namely 23 (2-(5-(azepan-1-yl)pentyloxy)-9H-xanthen-9-one) and 25 (2-(5-(azepan-1-yl)pentyloxy)-7-chloro-9H-xanthen-9-one), were especially very promising and showed high affinity for hH₃R (K_i = 170 nM and 100 nM respectively) and high inhibitory activity for acetylcholinesterase (IC₅₀ = 180 nM and 136 nM respectively). Moreover, these compounds showed moderate inhibitory activity for butyrylcholinesterase (IC₅₀ = 880 nM and 394 nM respectively) and hMAO B (IC₅₀ = 775 nM and 897 nM respectively). Furthermore, molecular docking studies were performed for hH₃R, human cholinesterases and hMAO B to describe the mode of interactions with these biological targets. Next, the two most promising compounds 23 and 25 were selected for in vivo studies. The results showed significant memory-enhancing effect of compound 23 in dizocilpine-induced amnesia in rats in two tests: step-through inhibitory avoidance paradigm (SIAP) and transfer latency paradigm time (TLPT). In addition, favourable analgesic effects of compound 23 were observed in neuropathic pain models. Therefore, compound 23 is a particularly promising structure for further design of new MTDLs for AD.

  DOI：

  10.1016/j.ejmech.2020.112743
• 作为产物：
  描述：

  4-氯-2-氟苯腈 在 aluminum (III) chloride 、 palladium diacetate 、 三溴化硼 、 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 23.17h， 生成 6-chloro-2-hydroxy-9H-xanthen-9-one
  参考文献：
  名称：

  AMINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES

  摘要：

  公开号：

  EP2842937B1

文献信息

• Polyarylenether mit Xanthoneinheiten, Verfahren zu ihrer Herstellung und ihre Verwendung
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0571883A1

  公开（公告）日：1993-12-01

  Polyarylenether, die Xanthoneinheiten enthalten und eine sehr hohe Temperaturbeständigkeit aufweisen, können aus preisgünstigen, gut zugänglichen Monomeren durch Polykondensation in basischem Medium unter im wesentlichen wasserfreien Bedingungen in Anwesenheit oder Abwesenheit eines aromatischen Lösemittels bei Temperaturen von 150 bis 400°C hergestellt werden. Hierbei kann man sowohl von Xanthon-Monomeren als auch von hydroxyhalogen-substituierten Benzophenon-Verbindungen ausgehen.

  聚芳醚含有氧杂蒽酮单元，具有极高的耐温性，可以用价格低廉、容易获得的单体，在基本无水的条件下，在有或没有芳香族溶剂的情况下，在 150 至 400°C 的温度下，在碱性介质中通过缩聚反应制得。黄酮单体和羟基卤代二苯甲酮化合物均可使用。
• US4954604A
  申请人：——

  公开号：US4954604A

  公开（公告）日：1990-09-04
• US5395914A
  申请人：——

  公开号：US5395914A

  公开（公告）日：1995-03-07
• US9657043B2
  申请人：——

  公开号：US9657043B2

  公开（公告）日：2017-05-23
• AMINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP2842937B1

  公开（公告）日：2018-01-17