1-(6-fluorobenzo[d]thiazol-2-yl)-3-phenylthiourea | 1266614-74-7

• 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: 1-(6-fluorobenzo[d]thiazol-2-yl)-3-phenylthiourea
• 英文别名: 1-(6-Fluoro-1,3-benzothiazol-2-yl)-3-phenylthiourea
• CAS: 1266614-74-7
• 化学式: C₁₄H₁₀FN₃S₂
• 分子量: 303.384
• InChiKey: WFWXBJKCIDMZBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 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：
  97.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(6-fluorobenzo[d]thiazol-2-yl)-3-phenylthiourea 在 1,3-di-n-butyl-1H-imidazol-3-ium tribromide 作用下， 反应 0.67h， 以83%的产率得到N-(benzo[d]thiazol-2-yl)-6-fluorobenzo[d]thiazol-2-amine
  参考文献：
  名称：

  1,3-二正丁基咪唑鎓三溴化物介导的苯并噻唑基氨基甲酸酯的化学选择性氧化环化：合成N-双-双-苯并噻唑衍生物的新方法

  摘要：

  发现4-（N，N-二甲基氨基）吡啶是使用2-氨基苯并噻唑和苯基异硫氰酸酯合成苯并噻唑基氨基甲酸酯衍生物的有效催化剂，在离子液体[bbim] [Br 3 ]于70°C处理后，独家提供形成的ñ -双-苯并噻唑以良好的收率衍生物。J.杂环化​​学。（2012）。

  DOI：

  10.1002/jhet.736
• 作为产物：
  描述：

  2-氨基-6-氟苯并噻唑 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 1-(6-fluorobenzo[d]thiazol-2-yl)-3-phenylthiourea
  参考文献：
  名称：

  6-Benzothiazolyl Ureas, Thioureas and Guanidines are Potent Inhibitors of ABAD/17β-HSD10 and Potential Drugs for Alzheimer"s Disease Treatment: Design, Synthesis and in vitro Evaluation

  摘要：

  背景：线粒体酶淀粉样β结合醇脱氢酶（ABAD），也称为17β-羟基甾体脱氢酶类型10（17β-HSD10），已被联系到阿尔茨海默病（AD）的发病机制中。ABAD/17β-HSD10是淀粉样β肽（Aβ）在线粒体基质内的结合位点，它会加剧Aβ的毒性。这两种蛋白质之间的相互作用触发了一系列事件，导致线粒体功能障碍，如在AD中所见。 方法：由于ABAD的酶活性是介导Aβ毒性所必需的，因此抑制ABAD提供了一种有希望的AD治疗方法。在本研究中，我们准备并评估了一系列新的苯并噻唑脲类似物，以确定它们抑制ABAD/17β-HSD10酶活性的效力。最有效的化合物也测试了其细胞毒性特性，并预测了它们穿透血脑屏障的能力。为了解释结构-活性关系，进行了定量构效关系（QSAR）和药效团研究。 结果与结论：化合物12被确定为最有希望的命中化合物，具有良好的抑制活性（IC50 = 3.06 ± 0.40 µM）和可接受的细胞毒性特征，与frentizole的母体化合物相当。令人满意的理化特性表明其能够穿透血脑屏障，使化合物12成为一种新颖的先导结构，适合进一步开发和生物评估。

  DOI：

  10.2174/1573406413666170109142725

文献信息

• Synthesis and cytotoxic evaluation of thiourea and N-bis-benzothiazole derivatives: A novel class of cytotoxic agents
  作者：Ravindra M. Kumbhare、Tulshiram Dadmal、Umesh Kosurkar、V. Sridhar、J. Venkateswara Rao

  DOI：10.1016/j.bmcl.2011.10.106

  日期：2012.1

  Benzothiazolyl thiocarbamides has been achieved using a catalytic amount of 4-dimethylaminopyridine (DMAP) followed by its chemoselective oxidative cyclization with 1,3-di-n-butylimidazolium tribromide[bbim][Br-3] to afford the N-bis-benzothiazole derivatives. All the synthesized compounds were evaluated for cytotoxic activity against two human monocytic cell lines (U 937, THP-1) and a mouse melanoma cell line (B16-F10). Based on their IC50 values, the majority of the benzothiazolyl thiocarbamides and N-bis-benzothiazoles had significant antiproliferative activity on U 937 and B16-F10 cells, the compounds 3b, 3e, 3f, 3k, 6c and 6h were found to be the most active. The present findings indicate clearly that the compound 3e exhibited more antiproliferative activity on U 937 cells than the standard molecule, etoposide. Nevertheless, these compounds have shown comparatively less cytotoxicity towards THP-1 cells. (C) 2011 Elsevier Ltd. All rights reserved.
• 6-Benzothiazolyl Ureas, Thioureas and Guanidines are Potent Inhibitors of ABAD/17β-HSD10 and Potential Drugs for Alzheimer"s Disease Treatment: Design, Synthesis and in vitro Evaluation
  作者：Ondrej Benek、Lukas Hroch、Laura Aitken、Rafael Dolezal、Patrick Guest、Marketa Benkova、Ondrej Soukup、Karel Musil、Kamil Kuca、Terry K. Smith、Frank Gunn-Moore、Kamil Musilek

  DOI：10.2174/1573406413666170109142725

  日期：2017.5.5

  Background: The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer’s disease (AD). ABAD/17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβtoxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. Methods: As ABAD’s enzymatic activity is required for mediating Aβ toxicity, its inhibition presents a promising strategy for AD treatment. In this study, a series of new benzothiazolylurea analogues have been prepared and evaluated in vitro for their potency to inhibit ABAD/17β-HSD10 enzymatic activity. The most potent compounds have also been tested for their cytotoxic properties and their ability to permeate through blood-brain barrier has been predicted. To explain the structureactivity relationship QSAR and pharmacophore studies have been performed. Results and Conclusion: Compound 12 was identified being the most promising hit compound with good inhibitory activity (IC50 = 3.06 ± 0.40 µ M) and acceptable cytotoxicity profile comparable to the parent compound of frentizole. The satisfactory physical-chemical properties suggesting its capability to permeate through BBB make compound 12 a novel lead structure for further development and biological assessment.

  背景：线粒体酶淀粉样β结合醇脱氢酶（ABAD），也称为17β-羟基甾体脱氢酶类型10（17β-HSD10），已被联系到阿尔茨海默病（AD）的发病机制中。ABAD/17β-HSD10是淀粉样β肽（Aβ）在线粒体基质内的结合位点，它会加剧Aβ的毒性。这两种蛋白质之间的相互作用触发了一系列事件，导致线粒体功能障碍，如在AD中所见。 方法：由于ABAD的酶活性是介导Aβ毒性所必需的，因此抑制ABAD提供了一种有希望的AD治疗方法。在本研究中，我们准备并评估了一系列新的苯并噻唑脲类似物，以确定它们抑制ABAD/17β-HSD10酶活性的效力。最有效的化合物也测试了其细胞毒性特性，并预测了它们穿透血脑屏障的能力。为了解释结构-活性关系，进行了定量构效关系（QSAR）和药效团研究。 结果与结论：化合物12被确定为最有希望的命中化合物，具有良好的抑制活性（IC50 = 3.06 ± 0.40 µM）和可接受的细胞毒性特征，与frentizole的母体化合物相当。令人满意的理化特性表明其能够穿透血脑屏障，使化合物12成为一种新颖的先导结构，适合进一步开发和生物评估。
• 1,3-Di-n-butylimidazolium tribromide-mediated chemoselective oxidative cyclization of benzothiazoyl carbaimides: A novel approach toward the synthesis of N-bis-benzothiazole derivatives
  作者：Ravindra M. Kumbhare、Tulshiram Dadmal、Umesh Kosurkar、K. Vijay Kumar

  DOI：10.1002/jhet.736

  日期：2012.3

  4‐(N,N‐Dimethylamino)pyridine is found to be an efficient catalyst for the synthesis of benzothiazoyl carbaimide derivatives using 2‐aminobenzothiazoles and phenylisothiocyanates, which on treatment with ionic liquid [bbim][Br3] at 70°C afforded exclusive formation of N‐bis‐benzothiazole derivatives in good yield. J. Heterocyclic Chem., (2012).

  发现4-（N，N-二甲基氨基）吡啶是使用2-氨基苯并噻唑和苯基异硫氰酸酯合成苯并噻唑基氨基甲酸酯衍生物的有效催化剂，在离子液体[bbim] [Br 3 ]于70°C处理后，独家提供形成的ñ -双-苯并噻唑以良好的收率衍生物。J.杂环化​​学。（2012）。