2-(氯磺酰基)环己烯-1-羧酸乙酯 | 243984-26-1

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 磺酰卤
• 中文名称: 2-(氯磺酰基)环己烯-1-羧酸乙酯
• 英文名称: ethyl 2-(chlorosulfonyl)cyclohex-1-ene-1-carboxylate
• 英文别名: ethyl 2-chlorosulfonyl-1-cyclohexene-1-carboxylate；ethyl 2-(chlorosulfonyl)cyclohex-1-enecarboxylate；ethyl 2-chlorosulfonylcyclohexene-1-carboxylate
• CAS: 243984-26-1
• 化学式: C₉H₁₃ClO₄S
• 分子量: 252.719
• InChiKey: HNDUKOBQKAFGCT-UHFFFAOYSA-N

物化性质

• 熔点：
  32-33 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  347.6±42.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(氯磺酰基)环己烯-1-羧酸乙酯 在 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 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：

  2-(ethoxycarbonyl)cyclohex-1-ene-1-sulfonic acid 在 氯化亚砜 作用下， 反应 14.0h， 生成 2-(氯磺酰基)环己烯-1-羧酸乙酯
  参考文献：
  名称：

  抗炎化合物：N-苯基-环己烯基磺酰胺衍生物的合成与合理设计

  摘要：

  （±）-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.

  DOI：

  10.1002/poc.1575

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。
• PHARMACEUTICAL AGENT
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2018855A1

  公开（公告）日：2009-01-28

  The present invention provides an agent for the prophylaxis or treatment of complications after coronary-artery bypass surgery or cardiac diseases, autoimmune diseases, central nervous system diseases, inflammatory diseases, sepsis, severe sepsis or septic shock in a patient who undergoes coronary-artery bypass surgery, which comprises a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a compound represented by the formula (II): wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof, and an agent for the prophylaxis or treatment of sepsis and the like, as well as complications after coronary-artery bypass surgery, which is prepared for administration of ethyl (6R)-6-[(2-chloro-4-fluoroanilino)sulfonyl]-1-cyclohexene-1-carboxylate or a salt thereof or a prodrug thereof in a specific dose at a specific administration time.

  本发明提供了一种用于预防或治疗冠状动脉旁路手术或心脏疾病、自身免疫疾病、中枢神经系统疾病、炎症性疾病、败血症、重型败血症或脓毒性休克后并发症的药剂，该药剂包括由式(I)表示的化合物：其中每个符号如规范中定义，或由式(II)表示的化合物：其中每个符号如规范中定义，或其盐或前药，以及一种用于预防或治疗败血症等并发症及冠状动脉旁路手术后并发症的药剂，该药剂用于在特定剂量和特定给药时间内给予乙酸乙酯(6R)-6-[(2-氯-4-氟苯胺基)磺酰]-1-环己烯-1-羧酸乙酯或其盐或前药。
• [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）
• 一种2-(氯磺酰基)环己烷-1-烯甲酸乙酯衍生物的制备方法
  申请人：上海皓元医药股份有限公司

  公开号：CN113636960A

  公开（公告）日：2021-11-12

  本发明涉及一种2‑(氯磺酰基)环己烷‑1‑烯甲酸乙酯衍生物的制备方法，包括以下步骤：1)将式III化合物溶于有机溶剂中，在碱的存在下，反应得通式IV化合物；2)将式IV化合物加入N‑氯代丁二酰亚胺制备得到式I的化合物；其中R1为氢、C1‑6烷基或C3‑6环烷基；R2优选Tf三氟甲磺酰基，Ts对甲苯磺酰基或Ms甲磺酰基。本方法是一条全新的可工业化的合成路线，还提供式IV全新的中间体化合物。同时，该路线避免使用硫化氢和氯气，得到式I化合物纯度好，产品稳定性好，对制备Toll样受体4(TLR4)抑制剂药物具有很好的方法学意义。