6-(trifluoromethoxy)-1,3-benzothiazole-2-thiol | 235101-85-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 6-(trifluoromethoxy)-1,3-benzothiazole-2-thiol
• 英文别名: 6-(trifluoromethoxy)benzo[d]thiazole-2-thiol；SKA-5；6-trifluoromethoxy-2-mercaptobenzothiazole；6-(trifluoromethoxy)-3H-1,3-benzothiazole-2-thione
• CAS: 235101-85-6
• 化学式: C₈H₄F₃NOS₂
• 分子量: 251.253
• InChiKey: RBTZKWXZXZEIEF-UHFFFAOYSA-N

物化性质

• 熔点：
  234-235 °C
• 沸点：
  300.6±52.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 储存条件：
  储存温度应控制在2-8℃，需密闭并保持干燥。

反应信息

• 作为反应物：
  描述：

  6-(trifluoromethoxy)-1,3-benzothiazole-2-thiol 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 2,3-dihydro-9a-methylthio-7-trifluoromethoxy-thazolo<2,3-b>benzothiazole
  参考文献：
  名称：

  Riluzole Series. Synthesis and in Vivo “Antiglutamate” Activity of 6-Substituted-2-benzothiazolamines and 3-Substituted-2-imino-benzothiazolines

  摘要：

  Two series of analogues of riluzole, a blocker of excitatory amino acid mediated neurotransmission, have been synthesized: monosubstituted 2-benzothiazolamines and 3-substituted derivatives. Of all the compounds prepared in the first series, only 2-benzothiazolamines bearing alkyl, polyfluoroalkyl, or polyfluoroalkoxy substituents in the 6-position showed potent anticonvulsant activity against administration of glutamic acid in rats. The most active compounds displaying in vivo "antiglutamate" activity were the 6-OCF3 (riluzole), 6-OCF2CF3, 6-CF3, and 6-CF2CF3 substituted derivatives with ED50 values between 2.5 and 3.2 mg/kg i.p. Among the second series of variously substituted benzothiazolines, compounds as active as riluzole or up to 3 times more potent were identified in two series: benzothiazolines bearing a beta-dialkylaminoethyl moiety and compounds with an alkylthioalkyl chain and their corresponding sulfoxides and sulfones. The most potent derivatives were 2-imino-3-(2-methylthio)- and 2-imino-3-(2-methylsulfinyl)-ethyl-6-trifluoromethoxybenzothiazlines (61 and 64, ED50 = 10 and 1.1 mg/kg i.p., respectively). In addition, intraperitoneal administration of some of the best benzothiazolines protected mice from mortality produced by hypobaric hypoxia.

  DOI：

  10.1021/jm980202u
• 作为产物：
  描述：

  2-亚肼基-6-(三氟甲氧基)-2,3-二氢苯并[d]噻唑 在 氯化亚砜 、 硫酸 、 硫脲 作用下， 反应 25.0h， 生成 6-(trifluoromethoxy)-1,3-benzothiazole-2-thiol
  参考文献：
  名称：

  Riluzole Series. Synthesis and in Vivo “Antiglutamate” Activity of 6-Substituted-2-benzothiazolamines and 3-Substituted-2-imino-benzothiazolines

  摘要：

  Two series of analogues of riluzole, a blocker of excitatory amino acid mediated neurotransmission, have been synthesized: monosubstituted 2-benzothiazolamines and 3-substituted derivatives. Of all the compounds prepared in the first series, only 2-benzothiazolamines bearing alkyl, polyfluoroalkyl, or polyfluoroalkoxy substituents in the 6-position showed potent anticonvulsant activity against administration of glutamic acid in rats. The most active compounds displaying in vivo "antiglutamate" activity were the 6-OCF3 (riluzole), 6-OCF2CF3, 6-CF3, and 6-CF2CF3 substituted derivatives with ED50 values between 2.5 and 3.2 mg/kg i.p. Among the second series of variously substituted benzothiazolines, compounds as active as riluzole or up to 3 times more potent were identified in two series: benzothiazolines bearing a beta-dialkylaminoethyl moiety and compounds with an alkylthioalkyl chain and their corresponding sulfoxides and sulfones. The most potent derivatives were 2-imino-3-(2-methylthio)- and 2-imino-3-(2-methylsulfinyl)-ethyl-6-trifluoromethoxybenzothiazlines (61 and 64, ED50 = 10 and 1.1 mg/kg i.p., respectively). In addition, intraperitoneal administration of some of the best benzothiazolines protected mice from mortality produced by hypobaric hypoxia.

  DOI：

  10.1021/jm980202u

文献信息

• LEGO-Inspired Drug Design: Unveiling a Class of Benzo[<i>d</i>]thiazoles Containing a 3,4-Dihydroxyphenyl Moiety as Plasma Membrane H⁺-ATPase Inhibitors
  作者：Truong-Thanh Tung、Trong T. Dao、Marta G. Junyent、Michael Palmgren、Thomas Günther-Pomorski、Anja T. Fuglsang、Søren B. Christensen、John Nielsen

  DOI：10.1002/cmdc.201700635

  日期：2018.1.8

  2‐(benzo[d]thiazol‐2‐ylthio)‐1‐(3,4‐dihydroxyphenyl)ethanones was found to inhibit Pma1p, with the most potent IC50 value of 8 μm in an in vitro plasma membrane H+‐ATPase assay. These compounds were also found to strongly inhibit the action of proton pumping when Pma1p was reconstituted into liposomes. 1‐(3,4‐Dihydroxyphenyl)‐2‐((6‐(trifluoromethyl)benzo[d]thiazol‐2‐yl)thio)ethan‐1‐one (compound 38) showed

  真菌质膜H + -ATPase（Pma1p）是发现新的抗真菌剂的潜在目标。令人惊讶的是，没有针对靶向Pma1p的小分子的结构-活性关系研究的报道。本文中，我们公开了一种乐高启发性的片段组装策略，用于设计，合成和发现含有3,4-二羟基苯基部分作为潜在Pma1p抑制剂的苯并[ d ]噻唑。发现一系列2-（苯并[ d ]噻唑-2-基硫基）-1-（3,4-二羟基苯基）乙酮可抑制Pma1p，在体外质膜中最有效的IC 50值为8μm高+‐ATPase分析。当Pma1p重构为脂质体时，还发现这些化合物强烈抑制质子泵浦的作用。1-（3,4-二羟基苯基）-2-（（6-（三氟甲基）苯并[ d ]噻唑-2-基）硫基）乙酮-1（化合物38）对白色念珠菌和酿酒酵母（Saccharomyces cerevisiae），可以与体外抑制Pma1p的能力相关并得到证实。
• 2-AMINOPYRIDINE KINASE INHIBITORS
  申请人：Steinig Arno G.

  公开号：US20090197862A1

  公开（公告）日：2009-08-06

  2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, Flt3, FGFR3, Ab1, Aurora A, c-Src, IGF-1R, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.

  具有Formula I结构的2-氨基吡啶化合物，以及这些化合物的药用可接受的盐。Formula I的化合物抑制动物（包括人类）中的酪氨酸激酶酶活性，并可用于治疗和/或预防各种疾病和病况。特别地，本文披露的化合物是激酶抑制剂，特别是但不限于KDR、Tie-2、Flt3、FGFR3、Ab1、Aurora A、c-Src、IGF-1R、ALK、c-MET、RON、PAK1、PAK2和TAK1，并可用于治疗增生性疾病，如但不限于癌症。本发明还涉及一种包含Formula I化合物的药物组合物，或其药用可接受的盐，以及药用可接受的载体的药物组合物。本发明还涉及一种通过向患有由蛋白激酶活性介导的病症的患者投与上述药物组合物的治疗方法。
• A Convenient Metal-Free Method for the Synthesis of Benzothiazolethiones from o-Haloanilines and Carbon Disulfide
  作者：Chanjuan Xi、Peng Zhao、Fei Wang

  DOI：10.1055/s-0031-1289713

  日期：2012.5

  A convenient method has been developed for the preparation of a variety of 1,3-benzothiazole-2(3H)-thiones. The reaction proceeds from an o-haloaniline derivative and carbon disulfide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene at 80-140 ˚C to give the corresponding 1,3-benzothiazole-2(3H)-thione derivatives in good-to-excellent yields. cyclizations - heterocycles - benzothiazoles - amines

  已经开发了一种方便的方法来制备各种1,3-苯并噻唑-2（3 H）-硫酮。反应是在80-140℃下，在1,8-二氮杂双环[5.4.0]十一碳-7-烯存在下，由邻卤代苯胺衍生物和二硫化碳进行的，得到相应的1,3-苯并噻唑-2（3 H）-硫酮衍生物，收率良好。 环化-杂环-苯并噻唑-胺-二硫化碳-串联反应
• Metal-free synthesis of 2-mercaptobenzothiazoles and 6-(4-substituted-1H-1,2,3-triazol-1-yl)-2-mercaptobenzothiazoles <i>via</i> microwave-assisted synthesis pathway
  作者：Truong Thanh Tung、Luong Xuan Huy

  DOI：10.1080/00397911.2020.1761984

  日期：2020.7.2

  reported. Our condition provides a convenient protocol for the synthesis of a diverse collection of 2-mercaptobenzothiazoles and 6-(4-substituted-1H-1,2,3-triazol-1-yl)-2-mercaptobenzothiazoles with a very simple purification process. This report provides an alternative protocol for fast access to the wide range of compounds for sequence synthesis and biological studies. Graphical Abstract

  摘要 本文报道了一种简单、高效且不含金属的方法，可通过微波辅助途径以优异的收率制备 2-巯基苯并噻唑及其衍生物。我们的条件为合成各种 2-巯基苯并噻唑和 6-(4-取代-1H-1,2,3-三唑-1-基)-2-巯基苯并噻唑的集合提供了一个方便的协议，纯化过程非常简单。该报告提供了一种替代方案，可用于快速访问用于序列合成和生物学研究的各种化合物。图形概要
• 2-aminopyridine kinase inhibitors
  申请人：OSI Pharmaceuticals, LLC

  公开号：US08178668B2

  公开（公告）日：2012-05-15

  2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, Flt3, FGFR3, Ab1, Aurora A, c-Src, IGF-1R, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.

  具有I式结构的2-氨基吡啶化合物，以及这些化合物的药学上可接受的盐。I式化合物抑制动物（包括人类）中的酪氨酸激酶酶活性，并在治疗和/或预防各种疾病和病况方面有用。特别地，本文披露的化合物是激酶抑制剂，特别是但不限于KDR，Tie-2，Flt3，FGFR3，Ab1，Aurora A，c-Src，IGF-1R，ALK，c-MET，RON，PAK1，PAK2和TAK1，并可用于治疗增殖性疾病，例如但不限于癌症。本发明还涉及一种制备药物组合物的方法，该组合物包括I式化合物或其药学上可接受的盐的治疗有效量以及药学上可接受的载体。本发明还涉及一种通过向患有蛋白激酶活性介导的病症的患者投与上述药物组合物的治疗方法。