[[amino-(4-methoxyphenyl)methylidene]amino] 2-chloroacetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [[amino-(4-methoxyphenyl)methylidene]amino] 2-chloroacetate
• 化学式: C₁₀H₁₁ClN₂O₃
• 分子量: 242.662
• InChiKey: PMHQIWIEBANZJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [[amino-(4-methoxyphenyl)methylidene]amino] 2-chloroacetate 以 甲苯 为溶剂， 生成 5-氯甲基-3-(4-甲氧基苯基)-1,2,4-恶二唑
  参考文献：
  名称：

  乙酰胆碱酯酶抑制剂的设计，合成，生物学评估和对接研究：新型Ac啶酮1,2,4，恶二唑-1,2,3-三唑杂种

  摘要：

  在这项研究中，设计，合成并评估了新的a啶酮1,2,4，恶二唑1,2,3-三唑杂合体的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。在各种合成的化合物中，10-（（1-（（3-（4--甲氧基苯基）-1,2,4-恶二唑-5-基）甲基）-1 H -1,2,3-三唑-4-基）甲基）吖啶-9-（10 ħ） -酮10b中显示出最有效的抗乙酰胆碱酯酶活性（IC 50  = 11.55  μ米）是一样有效的利凡斯的明。对接结果也与体外结果高度吻合，证实了化合物10b的双重结合抑制活性。

  DOI：

  10.1111/cbdd.12609
• 作为产物：
  描述：

  4-甲氧基苯甲腈 在 盐酸羟胺 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 [[amino-(4-methoxyphenyl)methylidene]amino] 2-chloroacetate
  参考文献：
  名称：

  乙酰胆碱酯酶抑制剂的设计，合成，生物学评估和对接研究：新型Ac啶酮1,2,4，恶二唑-1,2,3-三唑杂种

  摘要：

  在这项研究中，设计，合成并评估了新的a啶酮1,2,4，恶二唑1,2,3-三唑杂合体的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。在各种合成的化合物中，10-（（1-（（3-（4--甲氧基苯基）-1,2,4-恶二唑-5-基）甲基）-1 H -1,2,3-三唑-4-基）甲基）吖啶-9-（10 ħ） -酮10b中显示出最有效的抗乙酰胆碱酯酶活性（IC 50  = 11.55  μ米）是一样有效的利凡斯的明。对接结果也与体外结果高度吻合，证实了化合物10b的双重结合抑制活性。

  DOI：

  10.1111/cbdd.12609

文献信息

• Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone-1,2,4-oxadiazole-1,2,3-triazole Hybrids
  作者：Maryam Mohammadi-Khanaposhtani、Mohammad Mahdavi、Mina Saeedi、Reyhaneh Sabourian、Maliheh Safavi、Mahnaz Khanavi、Alireza Foroumadi、Abbas Shafiee、Tahmineh Akbarzadeh

  DOI：10.1111/cbdd.12609

  日期：2015.12

  this study, novel acridone‐1,2,4‐oxadiazole‐1,2,3‐triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10‐((1‐((3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl)methyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)acridin‐9(10H)‐one 10b showed the most potent anti‐acetylcholinesterase activity (IC50 = 11.55 μm)

  在这项研究中，设计，合成并评估了新的a啶酮1,2,4，恶二唑1,2,3-三唑杂合体的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。在各种合成的化合物中，10-（（1-（（3-（4--甲氧基苯基）-1,2,4-恶二唑-5-基）甲基）-1 H -1,2,3-三唑-4-基）甲基）吖啶-9-（10 ħ） -酮10b中显示出最有效的抗乙酰胆碱酯酶活性（IC 50  = 11.55  μ米）是一样有效的利凡斯的明。对接结果也与体外结果高度吻合，证实了化合物10b的双重结合抑制活性。
• Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents
  作者：Maryam Mohammadi-Khanaposhtani、Mohammad Shabani、Mehrdad Faizi、Iraj Aghaei、Reza Jahani、Zainab Sharafi、Narges Shamsaei Zafarghandi、Mohammad Mahdavi、Tahmineh Akbarzadeh、Saeed Emami、Abbas Shafiee、Alireza Foroumadi

  DOI：10.1016/j.ejmech.2016.01.054

  日期：2016.4

  number of acridone-based oxadiazoles 11a–n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested

  已经合成了许多基于cri啶酮的恶二唑11a–n，它们对戊戊四唑（PTZ）和最大电击（MES）引起的癫痫发作具有抗惊厥作用。另外，通过旋转脚踏试验评估了它们的神经毒性。相对于标准药物苯巴比妥，大多数化合物表现出更好的抗惊厥活性和更高的安全性。在测试的衍生物中，ED 50值为2.08 mg / kg的化合物11l是PTZ测试中最有效的化合物。氟马西尼阻断了化合物11l的抗惊厥作用，表明苯二氮卓（BZD）受体参与了原型化合物11l的抗惊厥活性。同样，化合物11l与GABA A受体的BZD结合位点的对接研究证实了化合物11l与BZD受体的可能结合。
• The discovery of a selective, high affinity A2B adenosine receptor antagonist for the potential treatment of asthma
  作者：Jeff Zablocki、Rao Kalla、Thao Perry、Venkata Palle、Vaibhav Varkhedkar、Dengming Xiao、Anthony Piscopio、Tenning Maa、Art Gimbel、Jia Hao、Nancy Chu、Kwan Leung、Dewan Zeng

  DOI：10.1016/j.bmcl.2004.11.044

  日期：2005.2

  Adenosine has been suggested to play a role in asthma, possibly via activation of A(2B) adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A(2B) AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A(2B) AdoR antagonist with good selectivity (A(2B) AdoR K-i = 50 nM, selectivity A(1) > 200: A(2A) > 200: A(3) > 167). (C) 2004 Elsevier Ltd. All rights reserved.
• Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles
  作者：Denise M Cottrell、Jeffrey Capers、Manar M Salem、Kate DeLuca-Fradley、Simon L Croft、Karl A Werbovetz

  DOI：10.1016/j.bmc.2004.03.054

  日期：2004.6

  A series of 5-thiocyanatomethyl- and 5-alkyl-3-aryl-1,2,4-oxadiazoles were synthesized and evaluated for their activity against kinetoplastid parasites. Formation of the oxadiazole ring was accomplished through the reaction of benzamidoximes with acyl chlorides, while the thiocyanate group was inserted by reacting the appropriate 5-halomethyl oxadiazole with ammonium thiocyanate. The thiocyanate-containing compounds possessed low micromolar activity against Leishmania donovani and Trypanosoma brucei, while the 5-alkyl oxadiazoles were less active against these parasites. 3-(4-Chlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4b) displayed modest selectivity for L. donovani axenic amastigote-like parasites over J774 macrophages, PC3 prostate cancer cells, and Vero cells (6.4-fold, 3.8-fold, and 9.1-fold, respectively), while 3-(3,4-dichlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4h) showed 30-fold selectivity against Vero cells but was not selective against PC3 cells. In a murine model of visceral leishmaniasis, compound 4b decreased liver parasitemia caused by L. donovani by 48% when given in five daily i.v. doses at 5 mg/kg and by 61 % when administered orally for 5 days at 50 mg/kg. These results indicate that aromatic thiocyanates hold promise for the treatment of leishmanial infections if the selectivity of these compounds can be improved. (C) 2004 Elsevier Ltd. All rights reserved.
• Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors
  作者：Jin Cai、Hongtao Wei、Kwon Ho Hong、Xiaoqing Wu、Meng Cao、Xi Zong、Lushen Li、Chunlong Sun、Junqing Chen、Min Ji

  DOI：10.1016/j.ejmech.2015.04.002

  日期：2015.5

  Using Entinostat as a lead compound, 2-aminobenzamide and hydroxamate derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro anti-proliferative activities using the MTT-based assay against five human cancer cell lines including U937, A549, NCI-H661, MDA-MB-231 and HCT116. 2-Aminobenzamide series of compounds (10a-10j) demonstrated the most significant inhibition against human acute monocytic myeloid leukemia cell line U937, but no or poor activities against two human lung cancer cell lines. Furthermore, the target compounds were screened for their inhibitory activities against HDAC 1, 2, and 8. 2-Aminobenzamide derivatives (10) manifested a higher selectivity for HDAC 1 over HDAC 2, but were not active against HDAC 8. In contrast, most hydroxamate derivatives (11) inhibit HDAC 8 with lower IC50 values than SAHA and Entinostat. Docking study with selected compounds 10f and ha revealed that the compounds might bind tightly to the binding pockets in HDAC 2 and HDAC 8, respectively. The results suggest that they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting HDACs. (C) 2015 Elsevier Masson SAS. All rights reserved.