2-(4-fluorophenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1,5-benzothiazepine | 856660-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 2-(4-fluorophenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1,5-benzothiazepine
• 英文别名: 2-[2-(4-fluorophenyl)-2,3-dihydrobenzo[b][1,4]thiazepin-4-yl]phenol；2-[2-(4-Fluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4-yl]phenol；2-[2-(4-fluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4-yl]phenol
• CAS: 856660-85-0
• 化学式: C₂₁H₁₆FNOS
• 分子量: 349.429
• InChiKey: WCROIGSCNRRNSN-UHFFFAOYSA-N

物化性质

• 熔点：
  156 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  501.1±50.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  57.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1,5-benzothiazepine 在 lithium aluminium tetrahydride 作用下， 生成 C₂₁H₁₈FNOS
  参考文献：
  名称：

  Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by Molecular Field Topology Analysis

  摘要：

  A striking dual inhibition of enzymes α-glucosidase and butyrylcholinesterase by small drug-like molecules, including 1,4-disubstituted-1,2,3-triazoles, chalcones, and benzothiazepines, was rationalized with the help of Molecular Field Topology Analysis, a 3D QSAR technique similar to CoMFA. A common pharmacophore supported the concept of a link existing between type-2 diabetes mellitus and Alzheimer's disease. These findings will be instrumental for rational design of drug candidates for both of these conditions.

  DOI：

  10.1016/j.ejmech.2014.04.018
• 作为产物：
  描述：

  3-(4-氟苯基)-1-(2-羟基苯基)丙-2-烯-1-酮 、 2-氨基苯硫醇 在 C₂₂H₃₂N₄⁽²⁺⁾*2CF₃O₃S^(1-) 作用下， 反应 1.33h， 以90%的产率得到2-(4-fluorophenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1,5-benzothiazepine
  参考文献：
  名称：

  Di-cationic Ionic Liquid Catalyzed Synthesis of 1,5-Benzothiazepines

  摘要：

  一种简单优雅的方法已被开发用于合成1,5-苯并噻嗪，采用双阳离子液体作为溶剂和催化剂，通过在温和反应条件下使邻氨基硫醇与多种查尔酮反应。此外，还研究了催化剂的重复使用性，进行了三轮实验。所有反应被提出是通过1,4-共轭迈克尔加成反应，然后进行环状缩合反应。

  DOI：

  10.14233/ajchem.2018.20920

文献信息

• Efficient and Eco-friendly Syntheses of 1,5-Benzothiazepines and 1,5-Benzodiazepines Catalyzed by [<i>Hmim</i>][NO₃] under Mild Conditions
  作者：Hossein Loghmani-Khouzani、Panteha Tamjidi、Iraj Mohammadpoor-Baltork、Marzieh Yaeghoobi、Noorsaadah Abd. Rahman、Ahmad Reza Khosropour、Majid Moghadam、Shahram Tangestaninejad、Valiolah Mirkhani、Mohammad Hossein Habibi、Ayana Kashima、Takayoshi Suzuki

  DOI：10.1002/jhet.1827

  日期：2014.1

  Crystal structures of a new thiazepine and diazepine (seven‐membered rings) have also been determined and compared with thiazine (six‐membered ring). In this method, N‐methylimidazolium nitrate [Hmim][NO3] has been used as a catalyst that acts as an environmental friendly system.

  本文介绍了1,5-苯并噻氮杂类和1,5-苯并二氮杂类衍生物的合成方法和反应机理。在这项研究中，已经用新方法制备了36种噻嗪类和二氮杂品（大多数是新的），并通过分光镜方法对其结构进行了表征。还确定了新的噻氮平和二氮杂（七元环）的晶体结构，并将其与噻嗪（六元环）进行了比较。在此方法中，硝酸N甲基咪唑鎓盐[ Hmim ] [NO 3 ]被用作催化剂，对环境无害。
• In silico studies on 2,3-dihydro-1,5-benzothiazepines as cholinesterase inhibitors
  作者：Farzana Latif Ansari、Saima Kalsoom、Zaheer-ul-Haq、Zahra Ali、Farukh Jabeen

  DOI：10.1007/s00044-011-9754-6

  日期：2012.9

  In vitro studies on cholinesterase inhibitory potential on the three sets of 2,3-dihydro-1,5-benzothiazepines have been carried out. The compounds in Set 1 were unsubstituted on ring A, while those in Sets 2 and 3 had a 2'- and 3'-hydoxy substituent, respectively, in ring A. These studies revealed that they are mixed inhibitors of both AChE and BChE as reflected from their IC50 values. It was further observed that 3'-hydroxy substituted benzothiazepines (Set 3) were found to have stronger affinity for both AChE and BChE compared with those of Sets 1 and 2. Moreover, all the compounds in Set 3 were found to be stronger BChE inhibitors than AChE. These experimental observations were rationalized by conducting in silico studies using molecular docking tool of Molecular Operating Environment (MOE) software, thereby, a good correlation was observed between IC50 values and their binding interactions within the enzyme active site. We have observed that these interactions were electrostatic and hydrophobic in nature besides hydrogen bonding. The high BChE inhibitory potential of 3'-hydroxy substituted benzothiazepines was found to be cumulative effect of hydrogen bonding and pi-pi interactions between the ligand and BChE. These findings may serve as a guideline for synthesizing more potent ChE inhibitors for the treatment of Alzheimer's disease and related dementias.
• Ghotekarab; Joshia; Mandhane, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 9, p. 1267 - 1270
  作者：Ghotekarab、Joshia、Mandhane、Bhagata、Gill

  DOI：——

  日期：——
• Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by Molecular Field Topology Analysis
  作者：Farukh Jabeen、Polina V. Oliferenko、Alexander A. Oliferenko、Girinath G. Pillai、Farzana Latif Ansari、C. Dennis Hall、Alan R. Katritzky

  DOI：10.1016/j.ejmech.2014.04.018

  日期：2014.6

  A striking dual inhibition of enzymes α-glucosidase and butyrylcholinesterase by small drug-like molecules, including 1,4-disubstituted-1,2,3-triazoles, chalcones, and benzothiazepines, was rationalized with the help of Molecular Field Topology Analysis, a 3D QSAR technique similar to CoMFA. A common pharmacophore supported the concept of a link existing between type-2 diabetes mellitus and Alzheimer's disease. These findings will be instrumental for rational design of drug candidates for both of these conditions.
• Di-cationic Ionic Liquid Catalyzed Synthesis of 1,5-Benzothiazepines
  作者：Raghavendra Sakirolla、Krishnaji Tadiparthi、Marzieh Yaeghoobi、Noorsaadah Abd. Rahman

  DOI：10.14233/ajchem.2018.20920

  日期：——

  A simple and elegant method for the synthesis of 1,5-benzothiazepines has been developed using di-cationic liquid as a solvent cum catalyst by the reaction of o-aminothiophenol with a variety of chalcones under mild reaction conditions. Furthermore the reusability of the catalyst has also been studied for three cycles. All the reactions are proposed to proceed through a 1,4-conjugate Michael addition followed by a cyclo-condensation reaction.

  一种简单优雅的方法已被开发用于合成1,5-苯并噻嗪，采用双阳离子液体作为溶剂和催化剂，通过在温和反应条件下使邻氨基硫醇与多种查尔酮反应。此外，还研究了催化剂的重复使用性，进行了三轮实验。所有反应被提出是通过1,4-共轭迈克尔加成反应，然后进行环状缩合反应。