(2-ethyl)bistrifluoromethyl thiophenolmethylphosphoric acid ethyl ester | 934177-56-7

• 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: (2-ethyl)bistrifluoromethyl thiophenolmethylphosphoric acid ethyl ester
• 英文别名: 1-(Diethoxyphosphorylmethylsulfanyl)-3,5-bis(trifluoromethyl)benzene
• CAS: 934177-56-7
• 化学式: C₁₃H₁₅F₆O₃PS
• 分子量: 396.29
• InChiKey: VOLUVRGCYNTRSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2-ethyl)bistrifluoromethyl thiophenolmethylphosphoric acid ethyl ester 在 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  ISOTHIOCYANATE COMPOUND AND APPLICATION THEREOF

  摘要：

  本发明提供了一种异硫氰酸酯化合物及其应用。该化合物是一种芳基取代的异硫氰酸酯化合物，其具有一般式I的结构。本发明的异硫氰酸酯化合物在水中具有非常好的溶解性，对XPO1蛋白的抑制活性远远优于其他非芳基取代的同源化合物，副作用小，具有良好的生物安全性和生物利用度，非常适合临床应用。因此，该异硫氰酸酯化合物具有巨大的潜在市场空间和经济效益。

  公开号：

  US20180029979A1
• 作为产物：
  描述：

  碘甲基膦酸二乙酯 、 3,5-双(三氟甲基)苯硫酚 在 sodium hydride 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以90%的产率得到(2-ethyl)bistrifluoromethyl thiophenolmethylphosphoric acid ethyl ester
  参考文献：
  名称：

  Organocatalyst-mediated enantioselective intramolecular Michael addition of aldehydes to vinyl sulfones

  摘要：

  Chiral amines with a hydrogen bond donor promote the intramolecular conjugate addition of aldehydes to vinyl sulfones. Chiral cyclic sulfone-aldehydes are obtained in good yields with an ee of up to 82%. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2010.03.043

文献信息

• Isothiocyanate compounds and isothiocyanate XPO1 protein inhibitor drugs thereof
  申请人：DRIVINGFORCE THERAPEUTICS Co., Ltd.

  公开号：US10315990B2

  公开（公告）日：2019-06-11

  The present invention provides an isothiocyanate compound and its application. The compound is an aryl-substituted isothiocyanate compound that has a structure of the general formula I. The isothiocyanate compound of the present invention has very good solubility in water, far better inhibitory activity for XPO1 protein than other non-aryl substituted congeneric compounds, little side effects, and good biological safety and bioavailability, and is quite suitable for clinical application. Therefore, the isothiocyanate compound would have tremendous potential market space and economic benefits.

  本发明提供了一种异硫氰酸酯化合物及其应用。该化合物是一种具有通式 I 结构的芳基取代的异硫氰酸盐化合物。本发明的异硫氰酸盐化合物在水中的溶解性非常好，对 XPO1 蛋白的抑制活性远远优于其他非芳基取代的同族化合物，副作用小，生物安全性和生物利用度好，非常适合临床应用。因此，异硫氰酸酯化合物将具有巨大的潜在市场空间和经济效益。
• Small-Molecule Antagonist Targeting Exportin-1 via Rational Structure-Based Discovery
  作者：Xibao Tian、Jiali Gao、Meishuo Liu、Yuqin Lei、Fangjun Wang、Jin Chen、Peng Chu、Jiujiao Gao、Feida Long、Minzhi Liang、Xiangyu Long、Huiying Chu、Cuixia Liu、Xueliang Li、Qingxiang Sun、Guohui Li、Yongliang Yang

  DOI：10.1021/acs.jmedchem.9b01663

  日期：2020.4.23

  Exportin-1 (also named as CRM1) plays a prominent role in autoimmune disorders and has emerged as a potential therapeutic target for colitis. Here we report on the rational structure-based discovery of a small-molecule antagonist of exportin-1, LFS-829, with low-range nanomolar activities. The co-crystallographic structure, surface plasmon resonance binding assay, and cellbased phenotypic nuclear export functional assay validated that exportin-1 is a key target of LFS-829. Moreover, we demonstrated that the C528S mutation or the knockdown on exportin-1 can abolish the cellular activities of LFS-829. Strikingly, oral administration of LFS-829 can significantly reverse the pathological features of colitis model mice. We revealed that LFS-829 can attenuate dual NF-kappa B signaling and the Nrf2 cytoprotection pathway via targeting exportin-1 in colitis mice. Moreover, LFS-829 has a very low risk of cardiotoxicity and acute toxicity. Therefore, LFS-829 holds great promise for the treatment of colitis and may warrant translation for use in clinical trials.