1-(propyl-3-enamino)thiocarbonyl-(3S)-3-[(1R)-hydroxyethyl]azetidin-2-one | 1426255-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 1-(propyl-3-enamino)thiocarbonyl-(3S)-3-[(1R)-hydroxyethyl]azetidin-2-one
• 英文别名: (3S)-3-[(1R)-1-hydroxyethyl]-2-oxo-N-prop-2-enylazetidine-1-carbothioamide
• CAS: 1426255-42-6
• 化学式: C₉H₁₄N₂O₂S
• 分子量: 214.288
• InChiKey: HFDNIJROFDNMBF-RQJHMYQMSA-N

物化性质

• 沸点：
  328.7±44.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯乙基异氰酸酯 、 1-(propyl-3-enamino)thiocarbonyl-(3S)-3-[(1R)-hydroxyethyl]azetidin-2-one 在 C₁₆H₃₅O₄Ti^(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到[(1R)-1-[(3S)-2-oxo-1-(prop-2-enylcarbamothioyl)azetidin-3-yl]ethyl] N-(2-phenylethyl)carbamate
  参考文献：
  名称：

  An unprecedented reversible mode of action of β-lactams for the inhibition of human fatty acid amide hydrolase (hFAAH)

  摘要：

  A series of compound was prepared to clarify the reversible mechanism of beta-lactamic hFAAH inhibitors on the one hand, and to modulate some of their physicochemical parameters on the other hand. In particular, two compounds (4h and 4e) were designed to display a potential good leaving group on the crucial carbonyl with a view to possibly acylating the active serine of the hFAAH catalytic triad. Reversibility studies showed that these two compounds retain the reversible mode of inhibition, suggesting a noncovalent interaction between our beta-lactams and hFAAH. Finally, pharmacological evaluations of bioisosteres of the lead compound (4a, IC50 = 5.3 nM) revealed that log P values and PSA could be optimized without altering the FAAH inhibition (IC50 values from 3.65 nM to 70.9 nM). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.11.035
• 作为产物：
  描述：

  (1'R,3S)-3-<1'-<(tert-butyldimethylsilyl)oxy>ethyl>azetidin-2-one 在 盐酸 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 6.0h， 生成 1-(propyl-3-enamino)thiocarbonyl-(3S)-3-[(1R)-hydroxyethyl]azetidin-2-one
  参考文献：
  名称：

  An unprecedented reversible mode of action of β-lactams for the inhibition of human fatty acid amide hydrolase (hFAAH)

  摘要：

  A series of compound was prepared to clarify the reversible mechanism of beta-lactamic hFAAH inhibitors on the one hand, and to modulate some of their physicochemical parameters on the other hand. In particular, two compounds (4h and 4e) were designed to display a potential good leaving group on the crucial carbonyl with a view to possibly acylating the active serine of the hFAAH catalytic triad. Reversibility studies showed that these two compounds retain the reversible mode of inhibition, suggesting a noncovalent interaction between our beta-lactams and hFAAH. Finally, pharmacological evaluations of bioisosteres of the lead compound (4a, IC50 = 5.3 nM) revealed that log P values and PSA could be optimized without altering the FAAH inhibition (IC50 values from 3.65 nM to 70.9 nM). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.11.035

文献信息

• An unprecedented reversible mode of action of β-lactams for the inhibition of human fatty acid amide hydrolase (hFAAH)
  作者：Marion Feledziak、Catherine Michaux、Didier M. Lambert、Jacqueline Marchand-Brynaert

  DOI：10.1016/j.ejmech.2012.11.035

  日期：2013.2

  A series of compound was prepared to clarify the reversible mechanism of beta-lactamic hFAAH inhibitors on the one hand, and to modulate some of their physicochemical parameters on the other hand. In particular, two compounds (4h and 4e) were designed to display a potential good leaving group on the crucial carbonyl with a view to possibly acylating the active serine of the hFAAH catalytic triad. Reversibility studies showed that these two compounds retain the reversible mode of inhibition, suggesting a noncovalent interaction between our beta-lactams and hFAAH. Finally, pharmacological evaluations of bioisosteres of the lead compound (4a, IC50 = 5.3 nM) revealed that log P values and PSA could be optimized without altering the FAAH inhibition (IC50 values from 3.65 nM to 70.9 nM). (C) 2012 Elsevier Masson SAS. All rights reserved.