6-(phenyl)-7-methyl-9-ethyl-5,6-dihydro-2H-benzo[b][1,4]oxazocine-8-carboxylic acid ethyl ester | 1190367-16-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(phenyl)-7-methyl-9-ethyl-5,6-dihydro-2H-benzo[b][1,4]oxazocine-8-carboxylic acid ethyl ester
• 英文别名: 7-methyl-6,9-diphenyl-5,6-dihydro-2H-benzo[b][1,4]oxazocine-8-carboxylic acid ethyl ester；ethyl 7-methyl-6,9-diphenyl-2,5-dihydro-1,6-benzoxazocine-8-carboxylate
• CAS: 1190367-16-8
• 化学式: C₂₆H₂₅NO₃
• 分子量: 399.489
• InChiKey: FGSLICWBOQGBJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.93
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  38.77
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  5-allyloxy-4-(allyl-phenyl-amino)-3-methyl-biphenyl-2-carboxylic acid ethyl ester 在 Grubbs catalyst first generation 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到6-(phenyl)-7-methyl-9-ethyl-5,6-dihydro-2H-benzo[b][1,4]oxazocine-8-carboxylic acid ethyl ester
  参考文献：
  名称：

  High-yielding synthesis of Nefopam analogues (functionalized benzoxazocines) by sequential one-pot cascade operations

  摘要：

  通过级联烯胺胺化/异芳香化/烯丙基化和二烯或烯炔偏析等关键步骤的组合，实现了一种高效的胺/钌催化三步法合成奈福泮类似物。在这篇通讯中，我们发现了钌催化在含有游离胺的烯烃中的应用，而不会在原位形成盐。

  DOI：

  10.1039/b910397j

文献信息

• Unravelling the binding mechanism and protein stability of human serum albumin while interacting with nefopam analogues: a biophysical and<i>insilico</i>approach
  作者：Mahesh Gokara、Vidadala V. Narayana、Vineet Sadarangani、Shatabdi Roy Chowdhury、Sreelaxmi Varkala、Dhevalapally B. Ramachary、Rajagopal Subramanyam

  DOI：10.1080/07391102.2016.1216895

  日期：2017.7.27

  In this study, molecular binding affinity was investigated for Nefopam analogues (NFs), a functionalized benzoxazocine, with human serum albumin (HSA), a major transport protein in the blood. Its binding affinity and concomitant changes in its conformation, binding site and simulations were also studied. Fluorescence data revealed that the fluorescence quenching of HSA upon binding of NFs analogues is based on a static mechanism. The three analogues of NFs binding constants (K-A) are in the order of NF3>NF2>NF1 with values of 1.53 +/-.057x10(4), 2.16 +/-.071x10(4) and 3.6 +/-.102x10(5)M(-1), respectively. Concurrently, thermodynamic parameters indicate that the binding process was spontaneous, and the complexes were stabilized mostly by hydrophobic interactions, except for NF2 has one hydrogen bond stabilizes it along with hydrophobic interactions. Circular dichroism (CD) studies revealed that there is a decrease in -helix with an increase in -sheets and random coils signifying partial unfolding of the protein upon binding of NFs, which might be due to the formation of NFs-HSA complexes. Further, molecular docking studies showed that NF1, NF2 and NF3 bound to subdomains IIIA, IB and IIA through hydrophobic interactions. However, NF1 have additionally formed a single hydrogen bond with LYS 413. Furthermore, molecular simulations unveiled that NFs binding was in support with the structural perturbation observed in CD, which is evident from the root mean square deviation and R-g fluctuations. We hope our insights will provide ample scope for engineering new drugs based on the resemblances with NFs for enhanced efficacy with HSA.