2-amino-4-(4-methoxyphenyl)thiazole-5-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-amino-4-(4-methoxyphenyl)thiazole-5-carbonitrile
• 英文别名: 2-Amino-4-(4-methoxyphenyl)-1,3-thiazole-5-carbonitrile；2-amino-4-(4-methoxyphenyl)-1,3-thiazole-5-carbonitrile
• 化学式: C₁₁H₉N₃OS
• 分子量: 231.278
• InChiKey: QLDHIEBYHNCYOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-4-(4-methoxyphenyl)thiazole-5-carbonitrile 在 亚硝酸特丁酯 、 对甲苯磺酸 、 copper dichloride 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 5.5h， 生成 (Z)-2-(2-(1-(1-ethyl-5-(4-((3-hydroxyazetidin-1-yl)methyl)thiazol-2-yl)-1H-indol-3-yl)-2,2,2-trifluoroethylidene)hydrazinyl)-4-(4-methoxyphenyl)thiazole-5-carbonitrile
  参考文献：
  名称：

  Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects

  摘要：

  ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indolebased lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assembling the phenyl thiazole fragment to the indole skeleton of lead 1. After a systematic structure guided optimization, by cycling the phenyl thiazole to the compacted benzothiazole or decreasing the lipophilicity, two promising ATX inhibitors (9j and 25a) were identified with IC50 values of 2.1 nM and 19.0 nM, respectively. All compounds were tested a panel of cancer cell lines and a preliminary affinity on breast cancer cell lines (SI > 16.5) were observed which shed a light on their potential application of breast cancer relevant cases. Through a dedicated docking study, the intramolecular pseudo-ring within the trifluoroacetylhydrazone moiety played a significant role in constraining the binding poses of 9j and 25a. Finally, a binding free energy calculation was conducted to examine the contribution of different interactions in binding affinity. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112456
• 作为产物：
  描述：

  茴香酸乙酯 在 碘 、 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 4.0h， 生成 2-amino-4-(4-methoxyphenyl)thiazole-5-carbonitrile
  参考文献：
  名称：

  Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects

  摘要：

  ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indolebased lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assembling the phenyl thiazole fragment to the indole skeleton of lead 1. After a systematic structure guided optimization, by cycling the phenyl thiazole to the compacted benzothiazole or decreasing the lipophilicity, two promising ATX inhibitors (9j and 25a) were identified with IC50 values of 2.1 nM and 19.0 nM, respectively. All compounds were tested a panel of cancer cell lines and a preliminary affinity on breast cancer cell lines (SI > 16.5) were observed which shed a light on their potential application of breast cancer relevant cases. Through a dedicated docking study, the intramolecular pseudo-ring within the trifluoroacetylhydrazone moiety played a significant role in constraining the binding poses of 9j and 25a. Finally, a binding free energy calculation was conducted to examine the contribution of different interactions in binding affinity. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112456

文献信息

• TBHP/AIBN-Mediated Synthesis of 2-Amino-thioazoles from Active Methylene Ketones and Thiourea under Metal-free Conditions
  作者：Jiyun Sun、Huaibin Ge、Xiaohua Zhen、Xuechan An、Guangtao Zhang、Daisy Zhang-Negrerie、Yunfei Du、Kang Zhao

  DOI：10.1016/j.tet.2018.02.064

  日期：2018.4

  A new oxidative system of tert-butyl hydroperoxide (TBHP)/azodiisobutyronitrile (AIBN) has been used for the first time for a convenient, metal-free synthesis of substituted 2-aminothioazoles from active methylene ketone derivatives and thiourea. The reaction is postulated to proceed via an oxidative cyclization initiated by a radical process and followed by a condensation reaction.

  首次使用叔丁基过氧化氢（TBHP）/偶氮二异丁腈（AIBN）的新氧化系统，从活性亚甲基酮衍生物和硫脲方便，无金属地合成取代的2-氨基噻唑。假定该反应通过自由基过程引发的氧化环化进行，然后进行缩合反应。
• 一种合成2-氨基噻唑衍生物的方法
  申请人：天津大学

  公开号：CN107739350B

  公开（公告）日：2020-12-22

  本发明公开了一种合成2‑氨基噻唑衍生物的方法，步骤为：以α位带有吸电子取代基的酮类衍生物(I)与硫脲(II)为原料，以过氧叔丁醇为氧化剂，偶氮二异丁腈为自由基引发剂，在室温～回流的条件下，在溶剂甲醇中发生自由基偶联反应及脱水反应，生成2‑氨基噻唑衍生物(III)；反应式为：本发明利用非金属的偶氮二异丁腈和过氧叔丁醇的自由基氧化体系，避免了昂贵的过渡金属催化剂的使用，拓宽了底物的范围，使用羰基α位是吸电子取代基的底物即可，易离去基团不再是必须的。具有操作简单，反应原料以及反应试剂易得，收率较高等优点。
• Visible-Light-Promoted C(sp3)–H Bond Functionalization toward Aminothiazole Skeletons from Active Methylene Ketones and Thioureas
  作者：Haichang Guo、Lei Wang、Renhua Zheng、Xiurong Hu、Huajiang Jiang

  DOI：10.1055/a-2035-2873

  日期：——

  A novel and efficient visible-light-induced method is developed for the one-pot synthesis of functionalized 2-aminothiazoles from easily accessible active methylene ketone derivatives and different thioureas at room temperature. The mild reaction conditions, green chemistry, straightforward work-up, and high yields of the products make this procedure useful for the construction of 2-aminothiazole derivatives.

  摘要 开发了一种新颖高效的可见光诱导法，用于在室温下从容易获得的活性亚甲基酮衍生物和不同的硫脲类化合物中单锅合成功能化的 2-氨基噻唑。该方法反应条件温和、化学性质绿色、操作简便、产物收率高，因此可用于构建 2-氨基噻唑衍生物。
• Modulators of the adenosine A3 receptors
  申请人：PALOBIOFARMA, S.L.

  公开号：US10238637B2

  公开（公告）日：2019-03-26

  Modulators of adenosin A3 receptors of formula (I): And procedure for preparing these compounds. Other objectives of the present invention are to provide pharmaceutical compositions comprising an effective amount of these compounds and the use of the compounds for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of the adenosine A3 receptor.

  式 (I) 的腺苷 A3 受体调节剂： 以及制备这些化合物的程序。本发明的其他目的是提供包含有效量这些化合物的药物组合物，以及使用这些化合物制造治疗病理状况或疾病的药物，这些病理状况或疾病可通过调节腺苷 A3 受体得到改善。
• Adenosine A3 receptor modulators
  申请人：Palobiofarma, S.L.

  公开号：US10744125B2

  公开（公告）日：2020-08-18

  Modulators of the adenosine A3 receptors of formula (I): and process for preparing said compounds. Other aspects of the present invention are pharmaceutical compositions comprising an effective amount of said compounds and the use of said compounds in the preparation of a medicament for treating pathological conditions or diseases that can be improved by modulation of adenosine A3 receptors.

  式 (I) 的腺苷 A3 受体调节剂： 以及制备所述化合物的工艺。本发明的其他方面是包含有效量所述化合物的药物组合物，以及所述化合物在制备用于治疗可通过调节腺苷 A3 受体得到改善的病理状况或疾病的药物中的用途。