2-疏基环己烯-1-羧酸乙酯 | 54928-91-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-疏基环己烯-1-羧酸乙酯
• 英文名称: ethyl 2-mercaptocyclohex-1-ene-1-carboxylate
• 英文别名: 2-Mercapto-cyclohexen-(1)-carbonsaeure-ethylester；2-thioxo-cyclohexanecarboxylic acid ethyl ester；ethyl 2-mercapto-1-cyclohexene-1-carboxylate；2-mercaptocyclohex-1-enecarboxylic acid ethyl ester；ethyl 2-mercaptocyclohex-1-enecarboxylate；ethyl 2-sulfanylcyclohexene-1-carboxylate
• CAS: 54928-91-5
• 化学式: C₉H₁₄O₂S
• 分子量: 186.275
• InChiKey: VRFUJRRFOFCDOO-UHFFFAOYSA-N

物化性质

• 沸点：
  136-139 °C(Press: 15-16 Torr)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  27.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-疏基环己烯-1-羧酸乙酯 在 氯 、 溶剂黄146 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 0.83h， 生成 瑞沙托维
  参考文献：
  名称：

  Discovery of Novel and Potent Small-Molecule Inhibitors of NO and Cytokine Production as Antisepsis Agents:  Synthesis and Biological Activity of Alkyl 6-(N-Substituted sulfamoyl)cyclohex-1-ene-1-carboxylate

  摘要：

  To develop a new therapeutic agent for sepsis, screening of the Takeda chemical library was carried out using mouse macrophages stimulated with lipopolysaccharide (LPS) to identify a new class of small-molecule inhibitors of inflammatory mediator production. The lead compound 5a was discovered, from which a series of novel cyclohexene derivatives I bearing a sulfamoyl and ester group were designed, synthesized and tested for their inhibitory activity against nitric oxide (NO) production. Derivatives I were synthesized by the coupling of sulfonyl chlorides and anilines with concomitant double bond migration in the presence of triethylamine, and phenyl ring substitution and modification of the ester and cyclohexene moieties were carried out. Among the compounds synthesized, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-cyclohex-1-ene-1-carboxylate [(R)-(+)-5n, TAK-242] was found to exhibit the most potent suppressive activity for the production of not only NO but also inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by LPS-stimulated mouse macrophages with IC50 values of 1.8, 1.9 and 1.3 nM, respectively. It shows marked beneficial effects in vivo also. Intravenous administration of (R)-(+)-5n at doses of 0.1 mg/kg or more suppressed the production of NO and various cytokines [TNF-alpha, IL-6 and IL-1 beta] in the mouse endotoxin shock model. Furthermore, it protected mice from death dose-dependently and all mice survived at a dose of 3 mg/kg. The minimum effective dose to protect mice from lethality in this model was 0.3 mg/kg, which was consistent with those for inhibitory effects on the production of NO and cytokines. Compound (R)-(+)-5n is currently undergoing clinical trials for the treatment of sepsis.

  DOI：

  10.1021/jm050623t
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 反应 6.0h， 以90%的产率得到2-疏基环己烯-1-羧酸乙酯
  参考文献：
  名称：

  一种巯基烯酯类化合物的制备方法

  摘要：

  一种巯基烯酯类化合物的制备方法，本发明属于有机化学合成领域，为解决放大生产风险性高等问题，本发明提供的合成路线为三步反应：(1)将起始物料2‑酮甲酸乙酯类化合物与Tf2O(三氟甲磺酸酐)在碱及溶剂A的作用下，生成三氟甲磺酰基保护的烯醇中间体1；(2)再与硫代试剂发生取代反应得到中间体2；(3)中间体2再在脱保护试剂作用下脱保护得到目标产物3。本发明的有益效果在于：采用本发明制备巯基烯酯类化合物的方法，工艺新颖，避免使用硫化氢等有毒气体，提升工艺的整体安全性与环保性等效果，更适合放大生产，解决产业化难题。

  公开号：

  CN113135848A

文献信息

• [EN] DIRECTED CONJUGATION TECHNOLOGIES<br/>[FR] TECHNOLOGIES DE CONJUGAISON DIRIGÉE
  申请人：KLEO PHARMACEUTICALS INC

  公开号：WO2021102052A1

  公开（公告）日：2021-05-27

  Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.

  本公开提供了用于将各种感兴趣的分子与目标剂进行定点偶联的技术。在某些实施方式中，本公开利用目标结合分子以提供高偶联效率和选择性。在某些实施方式中，所提供的技术可用于制备抗体偶联物。
• Cycloalkene derivatives, process for producing the same, and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06495604B1

  公开（公告）日：2002-12-17

  The present invention provides a compound represented by the formula: wherein R represents an aliphatic hydrocarbon group optionally having substituents, an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents, a group represented by the formula: OR1 (wherein R1 represents a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents) or a group represented by the formula: wherein R1b represents a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents, R1c is, same with or different from R1b, a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents, R0 represents a hydrogen atom or an aliphatic hydrocarbon group, or R and R0 represents a bond with each other, Ar represents an aromatic hydrocarbon group optionally having substituents, and n is an integer of 1 to 4, or a salt thereof, which is a agent for preventing or treating diseases such as cardiac disease, autoimmune disease, septick shock, etc.

  本发明提供了一种由以下公式表示的化合物：其中R代表一个具有取代基的脂肪烃基、一个具有取代基的芳香烃基、一个具有取代基的杂环基、一个由公式表示的基团：OR1（其中R1代表氢原子或具有取代基的脂肪烃基）或一个由公式表示的基团：其中R1b代表氢原子或具有取代基的脂肪烃基，R1c与R1b相同或不同，代表氢原子或具有取代基的脂肪烃基，R0代表氢原子或脂肪烃基，或者R和R0彼此之间形成键结合，Ar代表具有取代基的芳香烃基，n为1至4的整数，或其盐，用作预防或治疗心脏病、自身免疫疾病、感染性休克等疾病的药物。
• [EN] SUBSTITUTED CYCLOHEXENES<br/>[FR] CYCLOHEXÈNES SUBSTITUÉS
  申请人：AUSPEX PHARMACEUTICALS INC

  公开号：WO2009015028A1

  公开（公告）日：2009-01-29

  Disclosed herein are deuterated derivatives of TAK-242 of Formula (I) which are modulators of TLR4 signalling pathway, pharmaceutical compositions thereof and methods of use thereof. Formula (I)

  本公开涉及TAK-242的二氘代衍生物，其化学式为（I），这些衍生物是TLR4信号通路的调节剂，以及其药物组合物和使用方法。化学式（I）
• SUBSTITUTED CYCLOHEXENES
  申请人：Gant Thomas G.

  公开号：US20090022706A1

  公开（公告）日：2009-01-22

  Disclosed herein are substituted cyclohexene TLR4 signaling pathway modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文披露了化学式I的取代环己烯TLR4信号通路调节剂，其制备方法，制药组合物以及使用方法。
• Synthesis and rational design of anti-inflammatory compounds: <i>N</i> -phenyl-cyclohexenyl sulfonamide derivatives
  作者：Gustavo R. Lloret、Álvaro Cunha Neto、Roberto Rittner、Michelle Bitencourt、Matheus P. Freitas、Nilton S. Aquino

  DOI：10.1002/poc.1575

  日期：2009.12

  The synthesis of (±)‐ethyl 6‐[N‐(2‐chloro‐4‐fluorophenyl)sulfamoyl]cyclohex‐1‐ene‐1‐carboxylate (5n) has been reproduced from a method previously described and served as the background for the preparation of a nitro derivative, potentially useful as an anti‐inflammatory agent. Furthermore, a structure‐based QSAR analysis of a series of N‐arylsulfamoyl congeners derived a highly predictive model for

  （±）-乙基6- [ N-（2-氯-4-氟苯基）氨磺酰基]环己-1-烯-1-羧酸酯（5n）的合成方法已从先前描述的方法中复制并作为背景硝基衍生物的制备，可能用作抗炎药。此外，对一系列N-芳基氨磺酰基同系物进行基于结构的QSAR分析，得出了关于NO和细胞因子产生的新型小分子抑制剂活性的高度预测模型，该模型的制备可以通过与上述类似的程序成功完成。版权所有©2009 John Wiley＆Sons，Ltd.