ethyl 5,5,7,7-tetramethyl-2-(4-(trifluoromethyl)benzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate

• 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: ethyl 5,5,7,7-tetramethyl-2-(4-(trifluoromethyl)benzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate
• 英文别名: Ethyl 5,5,7,7-tetramethyl-2-[[4-(trifluoromethyl)benzoyl]amino]-4,6-dihydrothieno[2,3-c]pyridine-3-carboxylate
• 化学式: C₂₂H₂₅F₃N₂O₃S
• 分子量: 454.513
• InChiKey: ZVZZKQXPJGKRJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  95.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  四甲基哌啶酮 在 sulfur 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 ethyl 5,5,7,7-tetramethyl-2-(4-(trifluoromethyl)benzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate
  参考文献：
  名称：

  Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused by Leishmania major

  摘要：

  大利什曼原虫（L. major）是一种原生动物寄生虫，可引起皮肤利什曼病。目前约有 1200 万人受到感染，年发病率为 130 万例。本研究的目的是合成一个小型的新型噻吩衍生物库，并评估其寄生活性和潜在的作用机制（MOA）。我们对噻吩分子 5A 进行了结构-活性关系（SAR）研究。总的来说，我们合成了 8 种 5A 的噻吩衍生物，并通过硅胶柱层析进行了纯化。在这八种类似物中，分子 5D 对利什曼原虫的体外活性最高（EC50 0.09 ± 0.02 µM），仅在 0.63 µM 时对细胞内原虫增殖的抑制率就超过了 75%，并且具有极佳的选择性。此外，5D 对大肠杆菌原体的作用与活性氧（ROS）的生成有关，而硅对接研究表明，5D 可能在抑制胰硫还原酶方面发挥作用。总之，结合对 5A 衍生物的 SAR 研究和体外评估，我们发现了新型分子 5D，它在体外抗利什曼病方面具有很强的活性，能产生 ROS 导致细胞死亡，但对哺乳动物细胞没有明显的细胞毒性。

  DOI：

  10.3390/molecules23071626

文献信息

• Antiparasitic Compositions and Methods Utilizing Substituted 5,5,7,7-Tetramethyl- 4,5,6,7-Tetrahydrothieno[2,3-C]Pyridine Derivatives
  申请人：Board of Regents, The University of Texas System

  公开号：US20160362420A1

  公开（公告）日：2016-12-15

  The present disclosure relates generally to systems, methods, and compounds for therapeutic use against parasitic infections. More particularly, the disclosure relates to anti-parasitic compounds, and methods for making and for using the anti-parasitic compounds, where the anti-parasitic compounds have the general formula: where X, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are defined more fully below.
• ANTIPARASITIC COMPOSITIONS AND METHODS UTILIZING SUBSTITUTED 5,5,7,7-TETRAMETHYL-4,5,6,7-TETRAHYDROTHIENO[2,3-C] PYRIDINE DERIVATIVES
  申请人：Skouta Rachid

  公开号：US20170349606A1

  公开（公告）日：2017-12-07

  The present disclosure relates generally to systems, methods, and compounds for therapeutic use against parasitic infections. More particularly, the disclosure relates to anti-parasitic compounds, and methods for making and for using the anti-parasitic compounds, where the anti-parasitic compounds have the general formula: where X, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are defined more fully below.
• US9988395B2
  申请人：——

  公开号：US9988395B2

  公开（公告）日：2018-06-05
• Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused by Leishmania major
  作者：Felipe Rodriguez、Eva Iniguez、Guadalupe Pena Contreras、Haidar Ahmed、Thadeu Costa、Rachid Skouta、Rosa Maldonado

  DOI：10.3390/molecules23071626

  日期：——

  Leishmania major (L. major) is a protozoan parasite that causes cutaneous leishmaniasis. About 12 million people are currently infected with an annual incidence of 1.3 million cases. The purpose of this study was to synthesize a small library of novel thiophene derivatives, and evaluate its parasitic activity, and potential mechanism of action (MOA). We developed a structure–activity relationship (SAR) study of the thiophene molecule 5A. Overall, eight thiophene derivatives of 5A were synthesized and purified by silica gel column chromatography. Of these eight analogs, the molecule 5D showed the highest in vitro activity against Leishmania major promastigotes (EC50 0.09 ± 0.02 µM), with an inhibition of the proliferation of intracellular amastigotes higher than 75% at only 0.63 µM and an excellent selective index. Moreover, the effect of 5D on L. major promastigotes was associated with generation of reactive oxygen species (ROS), and in silico docking studies suggested that 5D may play a role in inhibiting trypanothione reductase. In summary, the combined SAR study and the in vitro evaluation of 5A derivatives allowed the identification of the novel molecule 5D, which exhibited potent in vitro anti-leishmanial activity resulting in ROS production leading to cell death with no significant cytotoxicity towards mammalian cells.

  大利什曼原虫（L. major）是一种原生动物寄生虫，可引起皮肤利什曼病。目前约有 1200 万人受到感染，年发病率为 130 万例。本研究的目的是合成一个小型的新型噻吩衍生物库，并评估其寄生活性和潜在的作用机制（MOA）。我们对噻吩分子 5A 进行了结构-活性关系（SAR）研究。总的来说，我们合成了 8 种 5A 的噻吩衍生物，并通过硅胶柱层析进行了纯化。在这八种类似物中，分子 5D 对利什曼原虫的体外活性最高（EC50 0.09 ± 0.02 µM），仅在 0.63 µM 时对细胞内原虫增殖的抑制率就超过了 75%，并且具有极佳的选择性。此外，5D 对大肠杆菌原体的作用与活性氧（ROS）的生成有关，而硅对接研究表明，5D 可能在抑制胰硫还原酶方面发挥作用。总之，结合对 5A 衍生物的 SAR 研究和体外评估，我们发现了新型分子 5D，它在体外抗利什曼病方面具有很强的活性，能产生 ROS 导致细胞死亡，但对哺乳动物细胞没有明显的细胞毒性。