1-(6-fluorobenzo[d]thiazol-2-yl)-3-phenylurea | 1018223-15-8

• 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-phenylurea
• 英文别名: 1-(6-Fluoro-1,3-benzothiazol-2-yl)-3-phenylurea
• CAS: 1018223-15-8
• 化学式: C₁₄H₁₀FN₃OS
• 分子量: 287.317
• InChiKey: XJFGLJANTCBGJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 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：
  82.3
• 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-phenylurea 、 丙二酸 在 乙酰氯 作用下， 反应 4.0h， 以74%的产率得到1-(6-fluoro-1,3-benzothiazol-2-yl)-3-phenylhexahydro-2,4,6-pyrimidinetrione
  参考文献：
  名称：

  掺入苯并噻唑的巴比妥酸衍生物：合成和抗惊厥药筛选

  摘要：

  以取代苯胺为原料合成了一系列1-(6-取代-1,3-苯并噻唑-2-基)-3-(取代苯基)六氢-2,4,6-嘧啶三酮4a-t。这些化合物含有两种活性抗惊厥药效团，苯并噻唑和巴比妥酸。基于不同的光谱技术确认了化合物的结构。评价所有化合物的抗惊厥活性。三种化合物 4c、4d 和 4s 在最大电击癫痫试验 (MES) 和皮下戊四唑试验 (scPTZ) 中显示出有希望的抗惊厥活性。在进行最小运动损伤测试时，它们还显示出广泛的安全性。

  DOI：

  10.1002/ardp.200900002
• 作为产物：
  描述：

  2-氨基-6-氟苯并噻唑 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(6-fluorobenzo[d]thiazol-2-yl)-3-phenylurea
  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 of amide and urea derivatives of benzothiazole as Raf-1 inhibitor
  作者：Eun Young Song、Navneet Kaur、Mi-Young Park、Yinglan Jin、Kyeong Lee、Guncheol Kim、Ki Youn Lee、Jee Sun Yang、Jae Hong Shin、Ky-Youb Nam、Kyoung Tai No、Gyoonhee Han

  DOI：10.1016/j.ejmech.2007.10.008

  日期：2008.7

  A series of amide and urea derivatives of benzothiazole have been synthesized and evaluated for their antiproliferative profile in human SK-Hep-1 (liver), MDA-MB-231 (breast), and NUGC-3 (gastric) cell lines. Among them, compounds 1-2, 16-18, 23, and 25-26 had potent to moderate inhibitory activities. Further these compounds were investigated for their ability to inhibit Raf-1 activity. (c) 2007 Elsevier Masson SAS. All rights reserved.
• [EN] NEURODEGENERATIVE THERAPIES<br/>[FR] THÉRAPIES NEURODÉGÉNÉRATIVES
  申请人：LYTIX BIOPHARMA AS

  公开号：WO2015118026A1

  公开（公告）日：2015-08-13

  The present invention provides a compound of formula (I) wherein: Y represents a C or N atom which may be substituted or form a cyclic group with R'" but may not be a quaternary C atom; R' is -OR1, -CONH2, -CF3, F, -OH, -NO2, -CN or -OCOR1 in which R1, is C1-3 alkyl and each may be in the beta or gamma position; R" is C1-3 alkyl or H; and R'" is H or a group consisting of 1-12 non-hydrogen atoms and may be linear, branched and/or incorporate one or more cyclic groups, cyclic groups may be aromatic and/or heterocyclic and 2 or more cyclic groups may be linked or fused and each may be substituted; or a salt, hydrate or solvate of a compound of formula (I) for use in the treatment or prevention of a neurodegenerative disorder by inhibiting formation of neurofibrillary (tau) tangles and/or by inhibiting Dyrk 1A. The invention further relates to non-therapeutic uses of these compounds.
• 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。
• Benzothiazole Incorporated Barbituric Acid Derivatives: Synthesis and Anticonvulsant Screening
  作者：Nadeem Siddiqui、Waquar Ahsan

  DOI：10.1002/ardp.200900002

  日期：2009.8

  3‐benzothiazol‐2‐yl)‐3‐(substituted phenyl)hexahydro‐2,4,6‐pyrimidinetriones 4a–t were synthesized starting from substituted anilines. These compounds contained two active anticonvulsant pharmacophores, benzothiazole and barbituric acid. Structures of the compounds were confirmed on the basis of different spectroscopic techniques. All the compounds were evaluated for their anticonvulsant activity. Three

  以取代苯胺为原料合成了一系列1-(6-取代-1,3-苯并噻唑-2-基)-3-(取代苯基)六氢-2,4,6-嘧啶三酮4a-t。这些化合物含有两种活性抗惊厥药效团，苯并噻唑和巴比妥酸。基于不同的光谱技术确认了化合物的结构。评价所有化合物的抗惊厥活性。三种化合物 4c、4d 和 4s 在最大电击癫痫试验 (MES) 和皮下戊四唑试验 (scPTZ) 中显示出有希望的抗惊厥活性。在进行最小运动损伤测试时，它们还显示出广泛的安全性。