ChemDiv E843-1064

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ChemDiv E843-1064
• 英文别名: 7-(2-{3-[4-(Trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-YL}ethyl)-2H,5H,6H,7H,8H-[1,3]dioxolo[4,5-G]quinazoline-6,8-dione；7-[2-[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethyl]-5H-[1,3]dioxolo[4,5-g]quinazoline-6,8-dione
• 化学式: C₂₀H₁₃F₃N₄O₅
• mdl: MFCD14920846
• 分子量: 446.342
• InChiKey: WRMHXCBHWGQUMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  对三氟甲基苯腈 在 盐酸羟胺 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二甲基亚砜 、 苯 为溶剂， 反应 21.0h， 生成 ChemDiv E843-1064
  参考文献：
  名称：

  Computer-aided identification, synthesis, and biological evaluation of novel inhibitors for botulinum neurotoxin serotype A

  摘要：

  Botulinum neurotoxins (BoNTs) are among the most potent biological toxin known to humans, and are classified as Category A bioterrorism agents by the Centers for Disease Control and prevention (CDC). There are seven known BoNT serotypes (A-G) which have been thus far identified in literature. BoNTs have been shown to block neurotransmitter release by cleaving proteins of the soluble NSF attachment protein receptor (SNARE) complex. Disruption of the SNARE complex precludes motor neuron failure which ultimately results in flaccid paralysis in humans and animals. Currently, there are no effective therapeutic treatments against the neurotoxin light chain (LC) after translocation into the cytosols of motor neurons. In this work, high-throughput in silico screening was employed to screen a library of commercially available compounds from ZINC database against BoNT/A-LC. Among the hit compounds from the in silico screening, two lead compounds were identified and found to have potent inhibitory activity against BoNT/A-LC in vitro, as well as in Neuro-2a cells. A few analogs of the lead compounds were synthesized and their potency examined. One of these analogs showed an enhanced activity than the lead compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.040

文献信息

• Computer-aided identification, synthesis, and biological evaluation of novel inhibitors for botulinum neurotoxin serotype A
  作者：Yu-Han Gary Teng、William T. Berger、Natasha M. Nesbitt、Kunal Kumar、Trent E. Balius、Robert C. Rizzo、Peter J. Tonge、Iwao Ojima、Subramanyam Swaminathan

  DOI：10.1016/j.bmc.2015.07.040

  日期：2015.9

  Botulinum neurotoxins (BoNTs) are among the most potent biological toxin known to humans, and are classified as Category A bioterrorism agents by the Centers for Disease Control and prevention (CDC). There are seven known BoNT serotypes (A-G) which have been thus far identified in literature. BoNTs have been shown to block neurotransmitter release by cleaving proteins of the soluble NSF attachment protein receptor (SNARE) complex. Disruption of the SNARE complex precludes motor neuron failure which ultimately results in flaccid paralysis in humans and animals. Currently, there are no effective therapeutic treatments against the neurotoxin light chain (LC) after translocation into the cytosols of motor neurons. In this work, high-throughput in silico screening was employed to screen a library of commercially available compounds from ZINC database against BoNT/A-LC. Among the hit compounds from the in silico screening, two lead compounds were identified and found to have potent inhibitory activity against BoNT/A-LC in vitro, as well as in Neuro-2a cells. A few analogs of the lead compounds were synthesized and their potency examined. One of these analogs showed an enhanced activity than the lead compounds. (C) 2015 Elsevier Ltd. All rights reserved.