2-chloro-N-(4'-chloro-[1,1'-biphenyl]-4-yl)acetamide | 107517-17-9

• 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: 2-chloro-N-(4'-chloro-[1,1'-biphenyl]-4-yl)acetamide
• 英文别名: chloro-acetic acid-(4'-chloro-biphenyl-4-ylamide)；Chlor-essigsaeure-(4'-chlor-biphenyl-4-ylamid)
• CAS: 107517-17-9
• 化学式: C₁₄H₁₁Cl₂NO
• 分子量: 280.153
• InChiKey: AVWBTNLYSFTMGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4'-chloro-[1,1'-biphenyl]-4-yl)acetamide 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 一水合肼 、 溶剂黄146 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.25h， 生成 3-(5-{[(4'-chlorobiphenyl-4-yl)amino]carbonyl}-1,3,4-thiadiazol-2-yl)propanoic acid
  参考文献：
  名称：

  Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors: a case of free fatty acid receptor 1 agonists

  摘要：

  A set of 1,3,4-thiadiazole-2-carboxamides bearing a substituted biphenyl in the amide portion was synthesised and tested for agonistic activity towards free fatty acid receptor 1 (FFA1). The observed activity trends were impossible to rationalised based solely on the docking energy scores of Glide SP. On the contrary, when the phospholipid cell membrane bilayer was reconstructed around FFA1, it became apparent that inactive compounds displayed significant strained contacts with the membrane while for active compounds the strain was noticeably lower. These findings justify using the improved docking protocol for modelling GPCR-ligand interactions which uses the crystal structure of the receptor and a reconstructed portion of a cell membrane.

  DOI：

  10.1080/14756366.2021.1955874
• 作为产物：
  描述：

  4’-氯-[1,1’-联苯]-4-胺 、 氯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-chloro-N-(4'-chloro-[1,1'-biphenyl]-4-yl)acetamide
  参考文献：
  名称：

  Novel 3-Nitrotriazole-Based Amides and Carbinols as Bifunctional Antichagasic Agents

  摘要：

  3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14a-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.

  DOI：

  10.1021/jm5015742

文献信息

• Niwa, Tohoku Yakka Daigaku Kiyo, 1957, # 4, p. 31,36
  作者：Niwa

  DOI：——

  日期：——
• Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Ivan P. O’Shea、Shane R. Wilkinson、Marcel Kaiser、Eric Chatelain、Jean-Robert Ioset

  DOI：10.1016/j.bmc.2015.08.014

  日期：2015.10

  3-Nitro-1H-1,2,4-triazole-and 2-nitro-1H-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. All 3-nitrotriazole-based derivatives were extremely potent anti-Trypanosoma cruzi agents at sub nM concentrations and exhibited a high degree of selectivity for the parasite. The 2-nitroimidazole analogs were only moderately active against T. cruzi amastigotes and exhibited low selectivity. Both types of compound were active against Leishmania donovani axenic amastigotes with excellent selectivity for the parasite, whereas three 2-nitroimidazole-based analogs were also moderately active against infected macrophages. However, no compound demonstrated selective activity against Trypanosoma brucei rhodesiense. The most potent in vitro anti-T. cruzi compounds were tested in an acute murine model and reduced the parasites to an undetectable level after five days of treatment at 13 mg/kg/day. Such compounds are potential inhibitors of T. cruzi CYP51 and, being excellent substrates for the type I nitroreductase (NTR) which is specific to trypanosomatids, work as prodrugs and constitute a new generation of effective and more affordable antitrypanosomal agents. (C) 2015 Elsevier Ltd. All rights reserved.
• Niwa, Tohoku Yakka Daigaku Kiyo, 1957, # 4, p. 31,38
  作者：Niwa

  DOI：——

  日期：——