ethyl 2-(chlorosulfonyl)cyclohept-1-ene-1-carboxylate | 243984-28-3

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 磺酰卤
• 英文名称: ethyl 2-(chlorosulfonyl)cyclohept-1-ene-1-carboxylate
• 英文别名: ethyl 2-chlorosulfonyl-1-cycloheptene-1-carboxylate；Ethyl 2-chlorosulfonylcycloheptene-1-carboxylate
• CAS: 243984-28-3
• 化学式: C₁₀H₁₅ClO₄S
• 分子量: 266.746
• InChiKey: URXPMLQLQFJQNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 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：

  ethyl 2-(chlorosulfonyl)cyclohept-1-ene-1-carboxylate 、 2-氯-4-氟苯胺 生成 ethyl 7-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-1-cycloheptene-1-carboxylate
  参考文献：
  名称：

  Cycloalkene derivatives, process for producing the same, and use

  摘要：

  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。

  公开号：

  US06495604B1
• 作为产物：
  描述：

  2-氧代环庚烷甲酸乙酯 在 劳森试剂 、 氯化亚砜 、 sodium trioxoboran tetrahydrate 、 溶剂黄146 作用下， 生成 ethyl 2-(chlorosulfonyl)cyclohept-1-ene-1-carboxylate
  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

文献信息

• 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。
• Combination Drugs
  申请人：——

  公开号：US20040063685A1

  公开（公告）日：2004-04-01

  The present invention relates to a pharmaceutical agent containing an anti-sepsis drug (e.g., cycloalkene compound), and at least one kind of drug selected from the group consisting of an antibacterial agent, an antifungal agent, a non-steroidal antiinflammatory drug, a steroid and an anticoagulant in combination.

  本发明涉及一种药物制剂，其包含一种抗脓毒症药物（例如环烷化合物），并且与至少一种从抗菌药物、抗真菌药物、非甾体抗炎药、类固醇和抗凝剂中选择的药物组合使用。
• STABLE EMULSION COMPOSITION
  申请人：Asakawa Naoki

  公开号：US20100016381A1

  公开（公告）日：2010-01-21

  The present invention provides an emulsion composition comprising (A) a compound stable in an acidic range, and (B) a buffer, wherein the pH is adjusted from about 3.7 to about 5.5.

  本发明提供了一种乳液组合物，包括(A)在酸性范围内稳定的化合物和(B)缓冲剂，其中pH值调节在大约3.7到5.5之间。
• Stable emulsion compositions
  申请人：——

  公开号：US20030212114A1

  公开（公告）日：2003-11-13

  An emulsion composition containing a compound represented by the formula: 1 wherein R is 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: —OR 1 (wherein R 1 is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents) or a group represented by the formula: 2 wherein R 1b is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents, R 1c is the same as or different from R 1b and is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents, R 0 is a hydrogen atom or an aliphatic hydrocarbon group, or R and R 0 in combination represent a bond, Ar is an aromatic hydrocarbon group optionally having substituents 3 and the like, and n is an integer of 1 to 4, a salt thereof or a prodrug thereof, wherein the composition is adjusted to have a pH of not more than about 6, shows improved stability of the compound, a salt thereof or a prodrug thereof, and realizes expression of superior efficacy.

  一种乳液组合物，含有由以下公式表示的化合物： 其中R是脂肪族烃基，可选地具有取代基，芳香族烃基，可选地具有取代基，杂环基，可选地具有取代基，代表式为—OR1（其中R1是氢原子或可选地具有取代基的脂肪族烃基）的基团，或代表式为2的基团（其中R1b是氢原子或可选地具有取代基的脂肪族烃基，R1c与R1b相同或不同，是氢原子或可选地具有取代基的脂肪族烃基，R0是氢原子或脂肪族烃基，或R和R0组合表示键合），Ar是芳香族烃基，可选地具有取代基3等，n为1至4的整数，其盐或前药，其中该组合物的pH值调整为不超过约6，表现出改善化合物，其盐或前药的稳定性，并实现优越疗效的表达。