1-chloro-2-nitro-4-((E)-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)benzene | 301179-69-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 1-chloro-2-nitro-4-((E)-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)benzene
• 英文别名: 1-chloro-2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)benzene；(E)-1-(4-acetylpiperazin-1-yl)-3-(4-chloro-3-nitrophenyl)prop-2-en-1-one
• CAS: 301179-69-1
• 化学式: C₁₅H₁₆ClN₃O₄
• 分子量: 337.763
• InChiKey: KWNBQRNXNUOTEZ-HWKANZROSA-N

物化性质

• 沸点：
  600.3±55.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  86.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-chloro-2-nitro-4-((E)-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)benzene 在 sodium carbonate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 (2-dimethylaminophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide
  参考文献：
  名称：

  Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intracellular Adhesion Molecule-1 Interaction. 1. Identification of an Additional Binding Pocket Based on an Anilino Diaryl Sulfide Lead

  摘要：

  The interaction between leukocyte function-associated antigen-1 (LFA-1), a member of the beta (2)-integrin family of adhesion molecules, and intracellular adhesion molecule ICAM-1 (cd54) is thought to play a critical role in the inflammatory process. On the basis of an anilino diaryl sulfide screening lead 1, in combination with pharmacophore analysis of other screening hits, we have identified an adjacent binding pocket. Subsequently, a p-ethenylcarbonyl linker was discovered to be optimal for accessing this binding site. Solution-phase parallel synthesis enabled rapid optimization of the cinnamides for this pocket. In conjunction with fine-tuning of the diaryl substituents, we discovered a novel series of potent, nonpeptide inhibitors of LFA-1/ICAM-1 interaction, exemplified by A-286982 (28h), which has IC50 values of 44 and 35 nM in an LFA-1/ICAM-1 binding assay and LFA-l-mediated cellular adhesion assay, respectively.

  DOI：

  10.1021/jm0002782
• 作为产物：
  描述：

  1-乙酰哌嗪 、 4-氯-3-硝基肉桂酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 2.0h， 以91.6%的产率得到1-chloro-2-nitro-4-((E)-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)benzene
  参考文献：
  名称：

  Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds

  摘要：

  本发明涉及新型肉桂酰胺化合物，用于治疗炎症和免疫性疾病以及脑血管痉挛，以及含有这些化合物的药物组合物，以及在哺乳动物中抑制炎症或抑制免疫反应的方法。

  公开号：

  US20040116518A1

文献信息

• Cell adhesion-inhibiting antiinflammatory and immune-suppressive
  申请人：Abbott Laboratories

  公开号：US06110922A1

  公开（公告）日：2000-08-29

  The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases, to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.

  本发明涉及新型肉桂酰胺化合物，该化合物对于治疗炎症和免疫性疾病有用，还涉及包含这些化合物的制药组合物，以及抑制哺乳动物炎症或抑制免疫反应的方法。
• Cell adhesion-inhibiting anti-inflammatory and immune-suppressive compounds
  申请人：Abbott Laboratories

  公开号：EP1481968A2

  公开（公告）日：2004-12-01

  The present invention relates to cinnamide compounds of formula (I), in which at least one of R1 to R5 is a "cis-cinnamide" (a) or a "trans-cinnamide" (b) and the other variables are as defined in the claims, that are useful for treating inflammatory and immune diseases, to pharmaceutical compositions containing these compounds and to methods of inhibiting inflammation or suppressing immune response in a mammal.

  本发明涉及式（I）的肉桂酰胺化合物，其中 R1 至 R5 中至少有一个是 "顺式肉桂酰胺"（a）或 "反式肉桂酰胺"（b），其他变量如权利要求中所定义，本发明涉及可用于治疗炎症和免疫疾病的肉桂酰胺化合物、含有这些化合物的药物组合物以及抑制哺乳动物炎症或抑制免疫反应的方法。
• Discovery of Novel <i>p</i>-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 4. Structure−Activity Relationship of Substituents on the Benzene Ring of the Cinnamide
  作者：Martin Winn、Edward B. Reilly、Gang Liu、Jeffrey R. Huth、Hwan-Soo Jae、Jennifer Freeman、Zhonghua Pei、Zhili Xin、John Lynch、Jeff Kester、Thomas W. von Geldern、Sandra Leitza、Peter DeVries、Robert Dickinson、Donna Mussatto、Gregory F. Okasinski

  DOI：10.1021/jm0103108

  日期：2001.12.1

  We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activity over mono substitution on the ring. The best 2,3-substituents were chlorine and trifluoromethyl groups. Compounds 39 and 40 which contain two CF3 groups have IC50 values of 0.5 and 0.1 nM, respectively, in inhibiting JY8 cells expressing LFA-1 on their surface, from adhering to ICAM-1. The structure-activity relationship (SAR) was examined using an NMR based model of the LFA-1 I domain/compound 31 complex. One of our compounds (38) was able to reduce cell migration in two different in vivo experiments.
• USRE039197E1
  申请人：——

  公开号：——

  公开（公告）日：——
• CELL ADHESION-INHIBITING ANTIINFLAMMATORY AND IMMUNE-SUPPRESSIVE COMPOUNDS
  申请人：ABBOTT LABORATORIES

  公开号：EP1140814B1

  公开（公告）日：2005-05-25