dibutyl 1-naphthyl phosphate | 74536-90-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: dibutyl 1-naphthyl phosphate
• 英文别名: Phosphoric acid, dibutyl 1-Naphthalenyl ester；dibutyl naphthalen-1-yl phosphate
• CAS: 74536-90-6
• 化学式: C₁₈H₂₅O₄P
• 分子量: 336.368
• InChiKey: PLDKUKDLHVUHPY-UHFFFAOYSA-N

物化性质

• 沸点：
  417.8±18.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  萘酚 、 氯磷酸二正丁基酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以48%的产率得到dibutyl 1-naphthyl phosphate
  参考文献：
  名称：

  Synthesis, biochemical evaluation, and molecular modeling studies of aryl and arylalkyl di- n -butyl phosphates, effective butyrylcholinesterase inhibitors

  摘要：

  A series of dialkyl aryl phosphates and dialkyl arylalkyl phosphates were synthesized. Their inhibitory activities were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The di-n-butyl phosphate series consistently displayed selective inhibition of BChE over AChE. The most potent inhibitors of butyrylcholinesterase were di-n-butyl-3,5-dimethylphenyl phosphate (4b) [ICy = 1.0 0.4 LM] and di-n-butyl 2-naphthyl phosphate (5b) [K-t=1.9 0.4 I.L.M]. Molecular modeling was used to uncover three subsites within the active site gorge that accommodate the three substituents attached to the phosphate group. Phosphates 4b and 5b were found to bind to these three subsites in analogous fashion with the aromatic groups in both analogs being accommodated by the "lower region," while the lone pairs on the P=0 oxygen atoms were oriented towards the oxyanion hole. In contrast, din-butyl-3,4-dimethylphenyl phosphate (4a) [K = 9 111M], an isomer of 4b, was found to orient its aromatic group in the "upper left region" subsite as placement of this group in the "lower region" resulted in significant steric hindrance by a ridge-like region in this subsite. Future studies will be designed to exploit these features in an effort to develop inhibitors of higher inhibitory strength against butyrylcholinesterase. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.002

文献信息

• US4199461A
  申请人：——

  公开号：US4199461A

  公开（公告）日：1980-04-22
• Synthesis, biochemical evaluation, and molecular modeling studies of aryl and arylalkyl di- n -butyl phosphates, effective butyrylcholinesterase inhibitors
  作者：Kensaku Nakayama、Jason P. Schwans、Eric J. Sorin、Trina Tran、Jeannette Gonzalez、Elvis Arteaga、Sean McCoy、Walter Alvarado

  DOI：10.1016/j.bmc.2017.04.002

  日期：2017.6

  A series of dialkyl aryl phosphates and dialkyl arylalkyl phosphates were synthesized. Their inhibitory activities were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The di-n-butyl phosphate series consistently displayed selective inhibition of BChE over AChE. The most potent inhibitors of butyrylcholinesterase were di-n-butyl-3,5-dimethylphenyl phosphate (4b) [ICy = 1.0 0.4 LM] and di-n-butyl 2-naphthyl phosphate (5b) [K-t=1.9 0.4 I.L.M]. Molecular modeling was used to uncover three subsites within the active site gorge that accommodate the three substituents attached to the phosphate group. Phosphates 4b and 5b were found to bind to these three subsites in analogous fashion with the aromatic groups in both analogs being accommodated by the "lower region," while the lone pairs on the P=0 oxygen atoms were oriented towards the oxyanion hole. In contrast, din-butyl-3,4-dimethylphenyl phosphate (4a) [K = 9 111M], an isomer of 4b, was found to orient its aromatic group in the "upper left region" subsite as placement of this group in the "lower region" resulted in significant steric hindrance by a ridge-like region in this subsite. Future studies will be designed to exploit these features in an effort to develop inhibitors of higher inhibitory strength against butyrylcholinesterase. (C) 2017 Elsevier Ltd. All rights reserved.