5 methoxy-2-(4-thiazolyl)benzimidazole | 1614-04-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5 methoxy-2-(4-thiazolyl)benzimidazole
• 英文别名: 5-methoxythiabendazole；5-methoxy-2-thiazol-4-yl-1H-benzoimidazole；4-(6-methoxy-1H-benzimidazol-2-yl)-1,3-thiazole
• CAS: 1614-04-6
• 化学式: C₁₁H₉N₃OS
• 分子量: 231.278
• InChiKey: AQQVJVFNODBBKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5 methoxy-2-(4-thiazolyl)benzimidazole 在 吡啶盐酸盐 、 三乙胺三氧化硫 作用下， 以 吡啶 为溶剂， 生成 5-羟基噻苯咪唑硫酸盐
  参考文献：
  名称：

  噻苯达唑在绵羊中的代谢命运。

  摘要：

  DOI：

  10.1021/jm00334a002
• 作为产物：
  描述：

  噻唑-4-甲醛 、 4-甲氧基邻苯二胺 在 sodium metabisulfite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到5 methoxy-2-(4-thiazolyl)benzimidazole
  参考文献：
  名称：

  新型苯并咪唑衍生物和类似物靶向NLRP3炎性小体的合成与生物学评估。

  摘要：

  合成了一系列噻唑的苯并[d]咪唑类似物，并评估了它们对炎性体NLRP3（核苷酸结合结构域富含亮氨酸的重复序列，含有蛋白质家族，含有pyrin结构域的家族3，也称为冻菌素或NALP3）的抗炎活性。 。通过产生IL-1β鉴定了两种先导化合物TBZ-09和TBZ-21。在第二轮生物学评估中，以铅为基础，又合成了34种化合物，并研究了它们的体外抗炎活性。几种化合物被鉴定为可以以剂量依赖的方式降低IL-1β表达的抗炎药。初步的构效关系也总结在这里。

  DOI：

  10.3390/molecules22020213

文献信息

• Metabolism of thiabendazole and teratogenic potential of its metabolites in pregnant mice.
  作者：TOSHIE TSUCHIYA、AKIRA TANAKA、MASAMICHI FUKUOKA、MICHIO SATO、TSUTOMU YAMAHA

  DOI：10.1248/cpb.35.2985

  日期：——

  In connection with the teratogenic activity of thiabendazole (TBZ), the metabolic fate of 14C-TBZ in pregnant mice was studied by administration of the drug in olive oil and gum arabic as vehicles. Absorption of TBZ in the olive oil group occurred more rapidly than in the gum arabic group, and the maximum blood level in the former group was 7-fold higher than that in the latter group. 5-Hydroxylated TBZ (5-HY TBZ), its glucuronide and its sulfate were identified as urinary and fecal metabolites. A very small quantity of N-methyl TBZ was also identified for the first time in the urine and feces. The percentages of TBZ, 5-HY TBZ, and the glucuronide and sulfate of 5-HY TBZ in the urine were 12-15, 22-24, 28-29 and 30-31%, respectively. About 97% of the dose was excreted into the urine (60-62%) and the feces (34-37%) within 7 d in each group. In a limb bud cell culture system for the assay of teratogenic potential, the concentrations of TBZ, 5-HY TBZ and N-methyl TBZ necessary to reduce the amounts of cartilage proteoglycan by 50% were estimated to be about 0.09, 0.09 and 0.24 mM, respectively. However, the concentrations of 5-HY TBZ glucuronide and sulfate were over 2 mM. Consequently, teratogenesis caused by TBZ appeared to be induced by the high levels of direct-acting teratogens such as TBZ and 5-HY TBZ when olive oil was used as a vehicle.

  关于噻苯咪唑（TBZ）的致畸活性，我们以橄榄油和阿拉伯树胶为载体，研究了 14C-TBZ 在怀孕小鼠体内的代谢转归。橄榄油组对 TBZ 的吸收比阿拉伯树胶组更快，前者的最大血药浓度是后者的 7 倍。在尿液和粪便中发现了 5-羟基 TBZ（5-HY TBZ）、其葡萄糖醛酸苷和硫酸盐代谢物。在尿液和粪便中还首次发现了极少量的 N-甲基 TBZ。尿液中 TBZ、5-HY TBZ 以及 5-HY TBZ 的葡萄糖醛酸苷和硫酸盐的比例分别为 12-15%、22-24%、28-29% 和 30-31%。各组在 7 天内约有 97% 的剂量通过尿液（60-62%）和粪便（34-37%）排出体外。在用于检测致畸潜力的肢芽细胞培养系统中，将软骨蛋白多糖的数量减少 50%所需的 TBZ、5-HY TBZ 和 N-methyl TBZ 浓度估计分别约为 0.09、0.09 和 0.24 mM。但 5-HY TBZ 葡萄糖醛酸苷和硫酸盐的浓度超过 2 毫摩尔。因此，在使用橄榄油作为载体时，TBZ 导致的畸胎似乎是由高浓度的直接致畸剂（如 TBZ 和 5-HY TBZ）诱发的。
• Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents
  作者：Chao Zhang、Bo Zhong、Simin Yang、Liangkun Pan、Siwang Yu、Zhongjun Li、Shuchun Li、Bin Su、Xiangbao Meng

  DOI：10.1016/j.bmc.2015.03.085

  日期：2015.7

  Thiabendazole, already approved by FDA for oral use as an anti-fungal and anti-helminthic drug since 1967, has recently been repurposed as a vascular disrupting agent. By optimization of the structure of the lead compound, we successfully identified compound TBZ-19 and the new derivative is over 100-fold more potent than the lead compound against the growth of four different cell lines ( A549, HCT-116, HepG2 and HUVECs). The most potent two candidates TBZ-07 and TBZ-19, exhibiting moderate inhibitory cell proliferation activity, were also verified as anti-angiogenesis and vascular disrupting agents. Therefore, TBZ-07 and TBZ-19 would be promising candidates with vasculature targeting activity and merit further development. (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome
  作者：Liangkun Pan、Nan Hang、Chao Zhang、Yu Chen、Shuchun Li、Yang Sun、Zhongjun Li、Xiangbao Meng

  DOI：10.3390/molecules22020213

  日期：——

  synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family，pyrin domain-containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized

  合成了一系列噻唑的苯并[d]咪唑类似物，并评估了它们对炎性体NLRP3（核苷酸结合结构域富含亮氨酸的重复序列，含有蛋白质家族，含有pyrin结构域的家族3，也称为冻菌素或NALP3）的抗炎活性。 。通过产生IL-1β鉴定了两种先导化合物TBZ-09和TBZ-21。在第二轮生物学评估中，以铅为基础，又合成了34种化合物，并研究了它们的体外抗炎活性。几种化合物被鉴定为可以以剂量依赖的方式降低IL-1β表达的抗炎药。初步的构效关系也总结在这里。
• The Metabolic Fate of Thiabendazole in Sheep¹
  作者：Dominick J. Tocco、Rudolf P. Buhs、Horace D. Brown、Alexander R. Matzuk、Holly E. Mertel、Robert E. Harman、Nelson R. Trenner

  DOI：10.1021/jm00334a002

  日期：1964.7