2-(4-(3-(1-((benzyloxy)carbonyl)piperidine-3-carboxamido)phenyl)-1H-1,2,3-triazol-1-yl)acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-(3-(1-((benzyloxy)carbonyl)piperidine-3-carboxamido)phenyl)-1H-1,2,3-triazol-1-yl)acetic acid
• 英文别名: 2-[4-[3-[(1-Phenylmethoxycarbonylpiperidine-3-carbonyl)amino]phenyl]triazol-1-yl]acetic acid；2-[4-[3-[(1-phenylmethoxycarbonylpiperidine-3-carbonyl)amino]phenyl]triazol-1-yl]acetic acid
• 化学式: C₂₄H₂₅N₅O₅
• 分子量: 463.493
• InChiKey: BKUZECOHNGWTDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氨基苯乙炔 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2-(4-(3-(1-((benzyloxy)carbonyl)piperidine-3-carboxamido)phenyl)-1H-1,2,3-triazol-1-yl)acetic acid
  参考文献：
  名称：

  Bacterial versus human sphingosine-1-phosphate lyase (S1PL) in the design of potential S1PL inhibitors

  摘要：

  A series of potential active-site sphingosine-1-phosphate lyase (S1PL) inhibitors have been designed from scaffolds 1 and 2, arising from virtual screening using the X-ray structures of the bacterial (StS1PL) and the human (hS1PL) enzymes. Both enzymes are very similar at the active site, as confirmed by the similar experimental kinetic constants shown by the fluorogenic substrate RBM13 in both cases. However, the docking scoring functions used probably overestimated the weight of electrostatic interactions between the ligands and key active-site residues in the protein environment, which may account for the modest activity found for the designed inhibitors. In addition, the possibility that the inhibitors do not reach the enzyme active site should not be overlooked. Finally, since both enzymes show remarkable structural differences at the access channel and in the proximity to the active site cavity, caution should be taken when designing inhibitors acting around that area, as evidenced by the much lower activity found in StS1PL for the potent hS1PL inhibitor D. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.07.033

文献信息

• Bacterial versus human sphingosine-1-phosphate lyase (S1PL) in the design of potential S1PL inhibitors
  作者：Pol Sanllehí、José-Luis Abad、Josefina Casas、Jordi Bujons、Antonio Delgado

  DOI：10.1016/j.bmc.2016.07.033

  日期：2016.9

  A series of potential active-site sphingosine-1-phosphate lyase (S1PL) inhibitors have been designed from scaffolds 1 and 2, arising from virtual screening using the X-ray structures of the bacterial (StS1PL) and the human (hS1PL) enzymes. Both enzymes are very similar at the active site, as confirmed by the similar experimental kinetic constants shown by the fluorogenic substrate RBM13 in both cases. However, the docking scoring functions used probably overestimated the weight of electrostatic interactions between the ligands and key active-site residues in the protein environment, which may account for the modest activity found for the designed inhibitors. In addition, the possibility that the inhibitors do not reach the enzyme active site should not be overlooked. Finally, since both enzymes show remarkable structural differences at the access channel and in the proximity to the active site cavity, caution should be taken when designing inhibitors acting around that area, as evidenced by the much lower activity found in StS1PL for the potent hS1PL inhibitor D. (C) 2016 Elsevier Ltd. All rights reserved.