2-(2-噻吩)-2,3-二氢-1,5-苯并噻嗪-4(5h)-酮 | 5871-68-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 中文名称: 2-(2-噻吩)-2,3-二氢-1,5-苯并噻嗪-4(5h)-酮
• 英文名称: 2,3-dihydro-2-(2-thienyl)-1,5-benzothiazepin-4(5H)-one
• 英文别名: 2-(2-thienyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one；2-thiophen-2-yl-3,5-dihydro-2H-1,5-benzothiazepin-4-one
• CAS: 5871-68-1
• 化学式: C₁₃H₁₁NOS₂
• mdl: MFCD01927811
• 分子量: 261.368
• InChiKey: LPKPHUUDFDWNPG-UHFFFAOYSA-N

物化性质

• 熔点：
  159-161°
• 沸点：
  475.3±45.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.153
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-(2-噻吩)-2,3-二氢-1,5-苯并噻嗪-4(5h)-酮 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以89%的产率得到2-Thiophen-2-yl-2,3-dihydro-5H-benzo[b][1,4]thiazepine-4-thione
  参考文献：
  名称：

  Oxazep​​ines 和 Thiazepines，XXV：2,3-Dihydro-1,5-benzothiazepine-4 (5H) -ones 的化学转化

  摘要：

  2,3 - 二氢 - 1,5 - 苯并噻嗪 - 4 (5H) - 硫酮 13-22 通过适当的 2,3 - 二氢 - 1,5 - 苯并噻嗪 - 4 (5H) - 酮与劳森试剂反应制备. N-酰基（23-25）和N-烷基（26-28）衍生物也已合成。用3-氯过氧苯甲酸氧化得到亚砜29-32，以H2O2为氧化剂得到砜33-40。

  DOI：

  10.1002/ardp.19923251108
• 作为产物：
  描述：

  3-（2-噻嗯基）丙烯酸 、 2-氨基苯硫醇 在 四丁基氟化铵 作用下， 以 neat (no solvent) 为溶剂， 反应 24.0h， 以70%的产率得到2-(2-噻吩)-2,3-二氢-1,5-苯并噻嗪-4(5h)-酮
  参考文献：
  名称：

  四丁基氟化铵（TBAF）催化的高效一锅法合成1,5-苯并噻唑酮

  摘要：

  使用四丁基氟化铵（TBAF）作为催化剂，已经开发出一种实用且有效的高产率制备1,5-苯并噻唑酮衍生物的方法。这项研究不仅扩大了以前在底物范围上的工作，而且使人们对这种药物支架的化学有了更多的了解。

  DOI：

  10.1016/j.tetlet.2016.07.012

文献信息

• Catalytic Enantioselective Synthesis of Protecting-Group-Free 1,5-Benzothiazepines
  作者：Sara Meninno、Chiara Volpe、Alessandra Lattanzi

  DOI：10.1002/chem.201700837

  日期：2017.4.3

  2,3‐dihydro‐1,5‐benzothiazepinones, by an organocatalyzed sulfa‐Michael reaction of readily available α,β‐unsaturated N‐acyl pyrazoles with 2‐aminothiophenols followed by silica‐gel‐catalyzed lactamization, has been developed. The method proceeds under mild conditions at room temperature and it requires only 1 mol % catalyst loading, to give 2‐aryl/alkyl‐substituted 1,5‐benzothiazepines in generally

  通过容易获得的α，β-不饱和N-酰基吡唑与2-氨基硫酚的有机催化磺胺反应，通过一锅法制得N-未保护的2,3-二氢-1,5-苯并噻唑酮的一锅对映选择性路线已经开发了催化内酰胺化。该方法在室温下在温和的条件下进行，仅需加入1 mol％的催化剂，即可得到通常被以良好的收率和对映选择性进行的2-芳基/烷基取代的1,5-苯并噻嗪类。该方法用于抗抑郁药（R）-（-）-噻嗪酮的简短合成，代表了获取对映体富集的未保护的1,5-苯并噻嗪类的第一种方法，该方法可用于药物发现中的快速衍生化。
• Lancelot, Jean-Charles; Letois, Bertrand; Saturnino, Carmela, Organic Preparations and Procedures International, 1992, vol. 24, # 2, p. 204 - 208
  作者：Lancelot, Jean-Charles、Letois, Bertrand、Saturnino, Carmela、Caprariis, Paolo De、Robba, Max

  DOI：——

  日期：——
• Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3β inhibitors through virtual screening
  作者：Peng Zhang、Hai-Rong Hu、Zhao-Hui Huang、Jia-Yi Lei、Yong Chu、De-Yong Ye

  DOI：10.1016/j.bmcl.2012.09.043

  日期：2012.12

  Glycogen synthase kinase-3 beta (GSK-3 beta) is an important serine/threonine kinase that has been proved as a key target for neurodegenerative diseases and diabetes. Up to date, most of known inhibitors are bound to the ATP-binding pocket of GSK-3 beta, which might lead widespread effects due to the high homology between kinases. Recently, some of its non-ATP competitive inhibitors had been confirmed having therapeutical effects owing to their high selectivity. This finding opens a new pathway to study hopeful drugs for treatment of these diseases. However, it is still a challenge nowadays on how to efficiently find non-ATP competitors. Here, we successfully discovered a novel scaffold of benzothiazepinones (BTZs) as selective non-ATP competitive GSK-3 beta inhibitors through virtual screening approach. A 3D receptor model of substrate binding site of GSK-3 beta was constructed and applied to screen against drug-like Maybridge database through Autodock program. BTZ compounds were top ranked as efficient hits and were then synthesized for further screening. Among them, the representative compound 4j showed activity to GSK-3 beta (IC50: 25 mu M) in non-ATP competitive mechanism, and nearly no inhibitory effect on other 10 related protein kinases. Overall, the results point out that BTZ compounds might be useful in treatment of Alzheimer's disease and diabetes mellitus as novel GSK-3 beta inhibitors. It also suggests, on the other hand, that virtual screening would provide a valuable tool in combination with in vitro assays for the identification of novel selective and potent inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.
• Substituted 2,3-Dihydro-1,5-benzothiazepin-4(5H)-one and Related Compounds. II. A New Class of Antidepressants¹
  作者：John Krapcho、Chester F. Turk

  DOI：10.1021/jm00320a008

  日期：1966.3
• Design, synthesis and biological evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β)
  作者：Peng Zhang、Hai-Rong Hu、Shi-Hui Bian、Zhao-Hui Huang、Yong Chu、De-Yong Ye

  DOI：10.1016/j.ejmech.2012.09.021

  日期：2013.3

  Glycogen synthase kinase-3 beta (GSK-3 beta) plays a key role in type II diabetes and Alzheimer's diseases, to which non-ATP competitive inhibitors represent an effectively therapeutical approach due to their good specificity. Herein, a series of small molecules benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of GSK-3 beta have been designed and synthesized. The in vitro evaluation performed by luminescent assay showed most BTZ derivatives have inhibitory effects in micromolar scale. Among them compounds 61, 6t and 6v have the IC50 values of 25.0 mu M, 27.8 mu M and 23.0 mu M, respectively. Moreover 6v is devoid of any inhibitory activity in the assays to other thirteen protein kinases. Besides, SAR is analyzed and a hypothetical enzymatic binding mode is proposed by molecular docking study, which would be useful for new candidates design. (C) 2012 Elsevier Masson SAS. All rights reserved.