5-[2-(3-Chlorophenyl)-2-oxoethyl]-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4-one | 1428258-35-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-[2-(3-Chlorophenyl)-2-oxoethyl]-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4-one
• 英文别名: 5-[2-(3-chlorophenyl)-2-oxoethyl]-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4-one
• CAS: 1428258-35-8
• 化学式: C₂₃H₁₈ClNO₂S
• 分子量: 407.92
• InChiKey: RWVCJCCAGGIZTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  肉桂酸 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 5-[2-(3-Chlorophenyl)-2-oxoethyl]-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β)

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.09.021

文献信息

• 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.