4-methoxy-N-(4-(3-phenyl-1,2,4-oxadiazole-5-yl)phenyl)-benzamide | 931755-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-methoxy-N-(4-(3-phenyl-1,2,4-oxadiazole-5-yl)phenyl)-benzamide
• 英文别名: 4-methoxy-N-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)phenyl]benzamide
• CAS: 931755-63-4
• 化学式: C₂₂H₁₇N₃O₃
• mdl: MFCD14827280
• 分子量: 371.395
• InChiKey: WRTWPWUOVSSEIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯甲酰胺肟 在 吡啶 、 tin(II) chloride dihdyrate 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 34.0h， 生成 4-methoxy-N-(4-(3-phenyl-1,2,4-oxadiazole-5-yl)phenyl)-benzamide
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of Some Oxadiazole Derivatives as Novel Amide-Based Inhibitors of Soluble Epoxide Hydrolase

  摘要：

  可溶性环氧化物水解酶（sEH）在内源性化学介质的代谢中发挥着重要作用，这些介质参与血压和炎症的调节。尽管目前报道的最有效的sEH抑制剂主要是尿素衍生物，但这些化合物的药代动力学特征有限。为了改善理化特性，除了具有良好的效力外，开发了以噁二唑环作为新型次级药效团的非尿素类酰胺衍生物以针对sEH酶。大多数具有适当物理性质的新化合物在体外的sEH抑制活性与12-(3-氨基-1-基-脲基)-十二酸（AUDA）这一强效尿素类sEH抑制剂相当。最强效化合物（15c）的IC50值为0.43 nM。

  DOI：

  10.2174/1570180811666140220005530

文献信息

• New 1,2,4-oxadiazole derivatives with positive mGlu₄ receptor modulation activity and antipsychotic-like properties
  作者：Anna Stankiewicz、Katarzyna Kaczorowska、Ryszard Bugno、Aneta Kozioł、Maria H. Paluchowska、Grzegorz Burnat、Barbara Chruścicka、Paulina Chorobik、Piotr Brański、Joanna M. Wierońska、Beata Duszyńska、Andrzej Pilc、Andrzej J. Bojarski

  DOI：10.1080/14756366.2021.1998022

  日期：2022.12.31

  Considering the allosteric regulation of mGlu receptors for potential therapeutic applications, we developed a group of 1,2,4-oxadiazole derivatives that displayed mGlu4 receptor positive allosteric modulatory activity (EC50 = 282-656 nM). Selectivity screening revealed that they were devoid of activity at mGlu1, mGlu2 and mGlu5 receptors, but modulated mGlu7 and mGlu8 receptors, thus were classified as group III-preferring mGlu receptor agents. None of the compounds was active towards hERG channels or in the mini-AMES test. The most potent in vitro mGlu4 PAM derivative 52 (N-(3-chloro-4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)phenyl)picolinamide) was readily absorbed after i.p. administration (male Albino Swiss mice) and reached a maximum brain concentration of 949.76 ng/mL. Five modulators (34, 37, 52, 60 and 62) demonstrated significant anxiolytic- and antipsychotic-like properties in the SIH and DOI-induced head twitch test, respectively. Promising data were obtained, especially for N-(4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)picolinamide (62), whose effects in the DOI-induced head twitch test were comparable to those of clozapine and better than those reported for the selective mGlu4 PAM ADX88178.
• 1,2,4-oxadiazole derivatives as allosteric modulators of metabotropic glutamate receptors belonging to group III
  申请人：Instytut Farmakologii Polskiej Akademii Nauk

  公开号：EP2853532B1

  公开（公告）日：2020-12-09
• Design, Synthesis and Biological Evaluation of Some Oxadiazole Derivatives as Novel Amide-Based Inhibitors of Soluble Epoxide Hydrolase
  作者：Elham Zavareh、Mahdi Hedayati、Laleh Rad、Azin Kiani、Soraya Shahhosseini、Mehrdad Faizi、Sayyed Tabatabai

  DOI：10.2174/1570180811666140220005530

  日期：2014.5.31

  Soluble epoxide hydrolase (sEH) enzyme plays an important role in the metabolism of endogenous chemical mediators which are involved in the regulation of blood pressure and inflammation. Although the most reported potent sEH inhibitors are urea derivatives, these compounds have limited pharmacokinetic profile. In order to improve physicochemical properties, besides having favorable potency, amide non-urea derivatives with oxadiazole ring as a novel secondary pharmacophore against sEH enzyme were developed. Most of the novel compounds with appropriate physical properties, had comparable in vitro sEH inhibitory activity to 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a potent urea-based sEH inhibitor. The IC50 value of the most potent compound (15c) was 0.43 nM.

  可溶性环氧化物水解酶（sEH）在内源性化学介质的代谢中发挥着重要作用，这些介质参与血压和炎症的调节。尽管目前报道的最有效的sEH抑制剂主要是尿素衍生物，但这些化合物的药代动力学特征有限。为了改善理化特性，除了具有良好的效力外，开发了以噁二唑环作为新型次级药效团的非尿素类酰胺衍生物以针对sEH酶。大多数具有适当物理性质的新化合物在体外的sEH抑制活性与12-(3-氨基-1-基-脲基)-十二酸（AUDA）这一强效尿素类sEH抑制剂相当。最强效化合物（15c）的IC50值为0.43 nM。