3-(biphenyl-3-yl)-2-tert-butyl-6-(thien-3-yl)imidazo[1,2-b]pyridazine | 1443985-89-4

• 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: 3-(biphenyl-3-yl)-2-tert-butyl-6-(thien-3-yl)imidazo[1,2-b]pyridazine
• 英文别名: 2-Tert-butyl-3-(3-phenylphenyl)-6-(3-thienyl)imidazo[1,2-b]pyridazine；2-tert-butyl-3-(3-phenylphenyl)-6-thiophen-3-ylimidazo[1,2-b]pyridazine
• CAS: 1443985-89-4
• 化学式: C₂₆H₂₃N₃S
• 分子量: 409.555
• InChiKey: IVTJMGKFMGASMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-溴频哪酮 在 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 7.0h， 生成 3-(biphenyl-3-yl)-2-tert-butyl-6-(thien-3-yl)imidazo[1,2-b]pyridazine
  参考文献：
  名称：

  3-联苯基咪唑并[1,2- a ]吡啶或[1,2- b ]哒嗪及其类似物，新型黄病毒科抑制剂

  摘要：

  以Ttou 84为起点，设计了一类新型的咪唑并[1,2- a ]吡啶和咪唑并[1,2- b ]哒嗪联苯衍生物，以优化其对牛病毒性腹泻病毒复制的抑制作用（ BVDV）和丙型肝炎病毒（HCV）。选择药物调节的三个位点，即中央杂环核心结构上的位置2、3和6。在测试的49个类似物中，只有化合物18j（3-（2'-hydroxybiphen-3-yl）-2-（2-甲氧基苯基）-6-（thien-3-yl）咪唑并[1,2- b ]哒嗪在HCV复制子系统中显示抗病毒活性，使人联想到选择性抑制（抑制60-70％）。化合物4f（3-（联苯-3-基）-2-（4-氟苯基）-6-苯硫基咪唑并[1,2- a吡啶]被证明是BVDV复制的最有选择性的抑制剂，与瘟病毒复制的已知抑制剂没有或仅有很小的交叉耐药性。4f的交叉电阻谱可能表明4f与BPIP，VP32947，AG110或LZ37没有与相同的结合位点相互作用。从针对

  DOI：

  10.1016/j.ejmech.2013.03.054

文献信息

• A small-molecule cell-based screen led to the identification of biphenylimidazoazines with highly potent and broad-spectrum anti-apicomplexan activity
  作者：Espérance Moine、Caroline Denevault-Sabourin、Françoise Debierre-Grockiego、Laurence Silpa、Olivier Gorgette、Jean-Christophe Barale、Philippe Jacquiet、Fabien Brossier、Alain Gueiffier、Isabelle Dimier-Poisson、Cécile Enguehard-Gueiffier

  DOI：10.1016/j.ejmech.2014.10.057

  日期：2015.1

  An in vitro screening of the anti-apicomplexan activity of 51 compounds, stemming from our chemical library and from chemical synthesis, was performed. As a study model, we used Toxoplasma gondii (T. gondii), expressing beta-galactosidase for the colorimetric assessment of drug activity on parasites cultivated in vitro. This approach allowed the validation of a new series of molecules with a biphenylimidazoazine scaffold as inhibitors of T. gondii growth in vitro. Hence, 8 molecules significantly inhibited intracellular replication of T. gondii in vitro, with EC50 < 1 mu M, while being non-toxic for human fibroblasts at these concentrations. Most attractive candidates were then selected for further biological investigations on other apicomplexan parasites (Neospora caninum, Besnoitia besnoiti, Eimeria tenella and Plasmodium falciparum). Finally, two compounds were able to inhibit growth of four different apicomplexans with EC50 in the submicromolar to nanomolar range, for each parasite. These data, including the broad anti-parasite spectrum of these inhibitors, define a new generation of potential anti-parasite compounds of wide interest, including for veterinary application. Studies realized on E. tenella suggest that these molecules act during the intracellular development steps of the parasite. Further experiments should be done to identify the molecular target(s) of these compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 3-Biphenylimidazo[1,2-a]pyridines or [1,2-b]pyridazines and analogues, novel Flaviviridae inhibitors
  作者：Cécile Enguehard-Gueiffier、Simone Musiu、Nicolas Henry、Jean-Baptiste Véron、Sylvie Mavel、Johan Neyts、Pieter Leyssen、Jan Paeshuyse、Alain Gueiffier

  DOI：10.1016/j.ejmech.2013.03.054

  日期：2013.6

  Using Ttou 84 as starting point, a novel class of biphenyl derivatives of imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine was designed to optimize the inhibitory properties on the replication of the bovine viral diarrhoea virus (BVDV) and hepatitis C virus (HCV). Three sites of pharmacomodulation were chosen i.e. positions 2, 3 and 6 on the central heterocyclic core structure. From the 49 analogues

  以Ttou 84为起点，设计了一类新型的咪唑并[1,2- a ]吡啶和咪唑并[1,2- b ]哒嗪联苯衍生物，以优化其对牛病毒性腹泻病毒复制的抑制作用（ BVDV）和丙型肝炎病毒（HCV）。选择药物调节的三个位点，即中央杂环核心结构上的位置2、3和6。在测试的49个类似物中，只有化合物18j（3-（2'-hydroxybiphen-3-yl）-2-（2-甲氧基苯基）-6-（thien-3-yl）咪唑并[1,2- b ]哒嗪在HCV复制子系统中显示抗病毒活性，使人联想到选择性抑制（抑制60-70％）。化合物4f（3-（联苯-3-基）-2-（4-氟苯基）-6-苯硫基咪唑并[1,2- a吡啶]被证明是BVDV复制的最有选择性的抑制剂，与瘟病毒复制的已知抑制剂没有或仅有很小的交叉耐药性。4f的交叉电阻谱可能表明4f与BPIP，VP32947，AG110或LZ37没有与相同的结合位点相互作用。从针对