4-(3-苯基-1,2,4-恶二唑-5-基)苯胺 | 54494-12-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(3-苯基-1,2,4-恶二唑-5-基)苯胺
• 英文名称: 4-(3-phenyl-1,2,4-oxadiazol-5-yl)aniline
• 英文别名: 3-Phenyl-5-p-aminophenyl-1,2,4-oxadiazol
• CAS: 54494-12-1
• 化学式: C₁₄H₁₁N₃O
• mdl: MFCD00445443
• 分子量: 237.261
• InChiKey: GUPGUFMJVVCPCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 4-(3-苯基-1,2,4-恶二唑-5-基)苯胺 在 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以90%的产率得到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
• 作为产物：
  描述：

  苯甲酰胺肟 在 sodiumsulfide nonahydrate 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 25.0h， 生成 4-(3-苯基-1,2,4-恶二唑-5-基)苯胺
  参考文献：
  名称：

  Relaxin-3/RXFP3 系统的第一个非肽拮抗剂的发现和表征

  摘要：

  神经肽松弛素 3/RXFP3 系统参与许多重要的生理过程，例如应激反应、食欲控制和奖赏动机。迄今为止，RXFP3 的药理学研究仅限于肽配体。在这项研究中，我们报告了通过高通量筛选活动发现的第一个 RXFP3 小分子拮抗剂。对命中化合物的集中构效关系研究导致 RLX-33 ( 33) 能够在一系列功能测定中抑制松弛素 3 的活性。RLX-33 对 RXFP3 的选择性高于松弛素/胰岛素超家族中的两个相关成员 RXFP1 和 RXFP4，并且具有用于行为评估的有利药代动力学特性。当对大鼠进行腹膜内给药时，RLX-33 可阻断由 RXFP3 选择性激动剂 R3/I5 诱导的食物摄入。总的来说，我们的研究结果表明，RLX-33 代表了一种有前途的拮抗剂支架，可用于开发靶向松弛素 3/RXFP3 系统的药物。

  DOI：

  10.1021/acs.jmedchem.2c00508

文献信息

• Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors
  作者：Zihao Hua、Howard Bregman、John L. Buchanan、Nagasree Chakka、Angel Guzman-Perez、Hakan Gunaydin、Xin Huang、Yan Gu、Virginia Berry、Jingzhou Liu、Yohannes Teffera、Liyue Huang、Bryan Egge、Renee Emkey、Erin L. Mullady、Steve Schneider、Paul S. Andrews、Lisa Acquaviva、Jennifer Dovey、Ankita Mishra、John Newcomb、Douglas Saffran、Randy Serafino、Craig A. Strathdee、Susan M. Turci、Mary Stanton、Cindy Wilson、Erin F. DiMauro

  DOI：10.1021/jm401317z

  日期：2013.12.27

  Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting β-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of APC-mutant colorectal cancer. Hit compound 8 was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound 8 leading to the identification of more potent and selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies.
• Synthesis and methemoglobinemia-inducing properties of benzocaine isosteres designed as humane rodenticides
  作者：Daniel Conole、Thorsten M. Beck、Morgan Jay-Smith、Malcolm D. Tingle、Charles T. Eason、Margaret A. Brimble、David Rennison

  DOI：10.1016/j.bmc.2014.02.013

  日期：2014.4

  A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia-with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed within each series, with 1,2,4-oxadiazole 3 (metHb% = 61.0 +/- 3.6) and 1,3,4-oxadiazole 10 (metHb% = 52.4 +/- 0.9) demonstrating the greatest activity. Of the 5 candidates (compounds 3, 10, 11, 13 and 23) evaluated in vivo, failure to induce a lethal end-point at doses of 120 mg/kg was observed in all cases. Inadequate metabolic stability, particularly towards hepatic enzymes such as the CYPs, was postulated as one reason for their failure. (C) 2014 Elsevier Ltd. All rights reserved.
• 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
• Antiparasitic agents. 6. Synthesis and anthelmintic activities of novel isothiocyanatophenyl-1,2,4-oxadiazoles
  作者：R. D. Haugwitz、A. J. Martinez、J. Venslavsky、R. G. Angel、B. V. Maurer、G. A. Jacobs、V. L. Narayanan、L. R. Cruthers、J. Szanto

  DOI：10.1021/jm00147a019

  日期：1985.9

  The syntheses and anthelmintic activities of 31 3- and 5-(isothiocyanatophenyl)-1,2,4-oxadiazoles are reported. In the primary anthelmintic screen, 3-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (39) showed 100% nematocidal activity and 3-(2-furanyl)-5-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (63), 3-(2-furanyl)-5-(2-chloro-4-isothiocyanatophenyl)-1,2,4-oxadiazole (64), and 3-(2-furanyl)-5-(4-chloro-3-isothiocyanatophenyl)-1,2,4-oxadiazole (66) showed 100% taeniacidal activity when administered orally to mice. The two most active members of this series, 39 and 63, were active against the gastrointestinal nematodes of sheep at 100 mg/kg. In addition, 39 was also found to be active against hookworms in dogs at a single, oral dose of 200 mg/kg.