4-chloro-2-(5-(2-methylfuran-3-yl)-1,3,4-oxadiazol-2-yl)phenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-chloro-2-(5-(2-methylfuran-3-yl)-1,3,4-oxadiazol-2-yl)phenol
• 英文别名: 4-Chloro-2-[5-(2-methylfuran-3-yl)-1,3,4-oxadiazol-2-yl]phenol；4-chloro-2-[5-(2-methylfuran-3-yl)-1,3,4-oxadiazol-2-yl]phenol
• 化学式: C₁₃H₉ClN₂O₃
• 分子量: 276.679
• InChiKey: GNJNNVNXHGSMAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 在 2-chloro-1,3-dimethyl imidazolium chloride 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.25h， 生成 4-chloro-2-(5-(2-methylfuran-3-yl)-1,3,4-oxadiazol-2-yl)phenol
  参考文献：
  名称：

  Discovery of Potent Inhibitors of Schistosoma mansoni NAD⁺ Catabolizing Enzyme

  摘要：

  The blood fluke Schistosoma mansoni is the causative agent of the intestinal form of schistosomiasis (or bilharzia). Emergence of Schistosoma mansoni with reduced sensitivity to praziquantel, the drug currently used to treat this neglected disease, has underlined the need for development of new strategies to control schistosomiasis. Our ability to screen drug libraries for antischistosomal compounds has been hampered by the lack of validated S. mansoni targets. In the present work, we describe a virtual screening approach to identify inhibitors of S. mansoni NAD(+) catabolizing enzyme (SmNACE), a receptor enzyme suspected to be involved in immune evasion by the parasite at the adult stage. Docking of commercial libraries into a homology model of the enzyme has led to the discovery of two in vitro micromolar inhibitors. Further structureactivity relationship studies have allowed a 3-log gain in potency, accompanied by a largely enhanced selectivity for the parasitic enzyme over the human homologue CD38.

  DOI：

  10.1021/acs.jmedchem.5b00203

文献信息

• Discovery of Potent Inhibitors of <i>Schistosoma mansoni</i> NAD⁺ Catabolizing Enzyme
  作者：Sylvain A. Jacques、Isabelle Kuhn、Oleksandr Koniev、Francis Schuber、Frances E. Lund、Alain Wagner、Hélène Muller-Steffner、Esther Kellenberger

  DOI：10.1021/acs.jmedchem.5b00203

  日期：2015.4.23

  The blood fluke Schistosoma mansoni is the causative agent of the intestinal form of schistosomiasis (or bilharzia). Emergence of Schistosoma mansoni with reduced sensitivity to praziquantel, the drug currently used to treat this neglected disease, has underlined the need for development of new strategies to control schistosomiasis. Our ability to screen drug libraries for antischistosomal compounds has been hampered by the lack of validated S. mansoni targets. In the present work, we describe a virtual screening approach to identify inhibitors of S. mansoni NAD(+) catabolizing enzyme (SmNACE), a receptor enzyme suspected to be involved in immune evasion by the parasite at the adult stage. Docking of commercial libraries into a homology model of the enzyme has led to the discovery of two in vitro micromolar inhibitors. Further structureactivity relationship studies have allowed a 3-log gain in potency, accompanied by a largely enhanced selectivity for the parasitic enzyme over the human homologue CD38.