4'-N,N-dimethylaminocinnamic acid chloride | 39145-43-2

• 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: 4'-N,N-dimethylaminocinnamic acid chloride
• 英文别名: 3t-(4-dimethylamino-phenyl)-acryloyl chloride；(E)-3-[4-(dimethylamino)phenyl]prop-2-enoyl chloride
• CAS: 39145-43-2
• 化学式: C₁₁H₁₂ClNO
• 分子量: 209.675
• InChiKey: JZWPRCWBKDCVNH-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4'-N,N-dimethylaminocinnamic acid chloride 在 一水合肼 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 9.0h， 生成 1-acetyl-5-(4-dimethylamino-phenyl)-3-(2-phenyl-oxazolo[4,5-b]phenoxazin-5-yl)-4,5-dihydro-1H-pyrazole
  参考文献：
  名称：

  Osman,A.M. et al., Journal of the Indian Chemical Society, 1977, vol. 54, p. 394 - 398

  摘要：

  DOI：
• 作为产物：
  描述：

  p-dimethylaminocinnamic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 4'-N,N-dimethylaminocinnamic acid chloride
  参考文献：
  名称：

  新型 pleuromutilin 芳基丙烯酸酯衍生物的设计、合成和评价作为有前途的广谱抗生素，特别是用于对抗多重耐药革兰氏阴性菌

  摘要：

  耐药菌株的出现对传统抗生素提出了严峻的挑战，凸显了探索新型抗菌药物的紧迫性。为了解决这个问题，本研究以组合原理为指导，努力设计和合成一系列 pleuromutilin 芳香族丙烯酸酯衍生物。评价这些衍生物的抗菌活性和构效关系，大多数衍生物对革兰氏阳性菌和革兰氏阴性菌均表现出中等至极好的抗菌活性。在这些衍生物中，5g 表现出最强的抗菌活性，MIC（最小抑菌浓度）值范围为 1-32 μg/mL，对临床分离的耐药菌株的 MIC 值为 4-64 μg/mL。此外，5g 表现出可忽略不计的细胞毒性、卓越的抗支原体活性以及更大的扰乱细菌细胞膜的倾向。值得注意的是，5g 的给药导致 MRSA（耐甲氧西林金黄色葡萄球菌）感染小鼠的存活率增加，ED 50 （中位有效剂量）值为 9.04 mg/kg。这些结果表明 5g 作为临床治疗耐药细菌感染的抗菌药物具有进一步发展的潜力。

  DOI：

  10.1016/j.ejmech.2023.115653

文献信息

• Design, Synthesis and Cytotoxic Evaluation of Novel Imatinib Amide Derivatives that Target Abl Kinase
  作者：Ri-Sheng Yao、Qiu-Xiang Guan、Xiao-Qin Lu、Ban-Feng Ruan

  DOI：10.2174/1570180811666140812231519

  日期：2014.10.30

  Novel imatinib amide derivatives (a1-28, b1-9) were synthesized and evaluated for their biological activities. All compounds were characterized by 1H NMR, MS and elemental analysis. Among all the derivatives, compounds a4, a10, a21, b1 and b2 displayed the most significant ability of inhibiting K562 cell proliferation with the IC50 values of 0.67, 0.66, 0.65, 0.59 and 0.62 µM, respectively, indicating that these compounds were potent inhibitors of Bcr-Abl in leukemic K562 cells, comparable to the reference compound imatinib. Molecular docking study was performed to position compounds a21 and b1 into the active site of Abl to determine the probable binding modes.

  新型的伊马替尼酰胺衍生物（a1-28, b1-9）被合成并评估了它们的生物活性。所有化合物均通过1H NMR、质谱及元素分析进行了表征。在所有衍生物中，化合物a4、a10、a21、b1和b2显示出最强的抑制K562细胞增殖能力，其IC50值分别为0.67、0.66、0.65、0.59和0.62 µM，表明这些化合物是白血病K562细胞中Bcr-Abl的有效抑制剂，与参考化合物伊马替尼相当。分子对接研究用于将化合物a21和b1定位到Abl的活性位点，以确定可能的结合模式。
• Synthesis and Biological Evaluation of N-Cinnamoyl and Mandelate Metformin Analogues
  作者：V. Anitha Kumari、K. Bharathi、K. Prabhu、K. Ponnudurai

  DOI：10.14233/ajchem.2016.19633

  日期：——

  A series of N,N-dimethyl-N1-[3-(substituted phenyl)-1-oxo-2-propenyl]biguanides were synthesized by coupling a solution of metformin in pyridine with different cinnamoyl chloride derivatives in ether for 3 h in addition to synthesis of some five molecules of metformin-mandelates. All the synthesized cinnamoyl metformins and a few metformin-mandelates were characterized by IR, NMR and Mass spectroscopic techniques. All the synthesized compounds were also evaluated for their antioxidant activity by DPPH scavenging method and nitric oxide scavenging method. All the compounds exhibited good antioxidant activity.

  一系列N,N-二甲基-N1-[3-(取代苯基)-1-氧-2-丙烯酰基]双胍化合物是通过将甲福明在吡啶中的溶液与不同的肉桂酰氯衍生物在乙醚中反应3小时合成的，此外还合成了一些五种甲福明-扁桃酸盐。所有合成的肉桂酰甲福明和少数甲福明-扁桃酸盐均通过红外、核磁共振和质谱技术进行了表征。所有合成的化合物还通过DPPH清除方法和一氧化氮清除方法评估了它们的抗氧化活性。所有化合物均显示出良好的抗氧化活性。
• Novel cephalosporin derivatives possessing a substituted cinnamoyl moiety at the 7β-position. Synthesis, structural characterization and antibacterial activity of 3-acetoxymethyl cephalosporin derivatives
  作者：Miguel A López、Zalua Rodríguez、Maritza González、Blanca Tolón、Rizette Avila、Ileana González、Leonor Garmendía、Taimirys Mamposo、Ramón Carrasco、Rolando Pellón、Hermán Vélez、Adamo Fini

  DOI：10.1016/j.ejmech.2004.02.016

  日期：2004.8

  Twenty 3-acetoxymethyl cephalosporin derivatives, with various cinnamoyl (3-phenyl-2-propenoyl) substituted groups at the 7beta-position, were synthesized and evaluated for antibacterial activity in vitro. Some of these cephalosporin derivatives showed good selective activity against Gram-positive bacteria. Although substitution on the aromatic ring of cinnamoyl moiety generally reduced antimicrobial

  合成了20个3-乙酰氧基甲基头孢菌素衍生物，在7β-位带有各种肉桂酰基（3-苯基-2-丙烯酰基）取代基，并在体外评估了其抗菌活性。这些头孢菌素衍生物中的一些对革兰氏阳性细菌显示出良好的选择性活性。尽管在肉桂酰基部分的芳环上的取代通常降低了对葡萄球菌sp的抗微生物活性。在对位的羟基，特别是邻，对二氯取代的肠球菌和肠球菌，提高了对金黄色葡萄球菌（MRSA）的耐甲氧西林菌株的活性。肉桂酰基部分的双键α位置上的取代也影响抗微生物活性。附着在该位置上的氰基增加了对阴性凝固酶葡萄球菌和肠球菌sp的活性。并将抗菌谱扩展到革兰氏阴性菌。
• Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents
  作者：Chih-Jung Kuo、Jiun-Jie Shie、Jim-Min Fang、Guei-Rung Yen、John T.-A. Hsu、Hun-Ge Liu、Sung-Nain Tseng、Shih-Cheng Chang、Ching-Yin Lee、Shin-Ru Shih、Po-Huang Liang

  DOI：10.1016/j.bmc.2008.06.015

  日期：2008.8

  Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond with the active site Cys residue. In this study, we have prepared the recombinant 3C protease from EV71 (TW/2231/98), a particular strain which causes severe outbreaks in Asia, and developed inhibitors against the protease and the viral replication. For inhibitor design, the P3 group of AG7088, which is not interacting with the rhinovirus protease, was replaced with a series of cinnamoyl derivatives directly linked to P2 group through an amide bond to simplify the synthesis. While the replacement caused decreased potency, the activity can be largely improved by substituting the alpha,beta-unsaturated ester with an aldehyde at the P1' position. The best inhibitor 10b showed EC(50) of 18 nM without apparent toxicity (CC(50) > 25 mu M). Our study provides potent inhibitors of the EV71 3C protease as anti-EV71 agents and facilitates the combinatorial synthesis of derivatives for further improving the inhibitory activity. (C) 2008 Elsevier Ltd. All rights reserved.
• <i>N</i>-Hydroxybenzimidazole Inhibitors of the Transcription Factor LcrF in <i>Yersinia</i>: Novel Antivirulence Agents
  作者：Oak K. Kim、Lynne K. Garrity-Ryan、Victoria J. Bartlett、Mark C. Grier、Atul K. Verma、Gabriel Medjanis、Janice E. Donatelli、Ann B. Macone、S. Ken Tanaka、Stuart B. Levy、Michael N. Alekshun

  DOI：10.1021/jm9006577

  日期：2009.9.24

  LcrF, a multiple adaptational response (MAR) transcription factor, regulates virulence in Yersinia pestis and Yersinia pseudotuberculosis. In a search for small molecule inhibitors of LcrF, an acrylic amide series of N-hydroxybenzimidazoles was synthesized and the SAR (structure-activity relationship) was examined, Selected test compounds demonstrated inhibitory activity in a primary cell-free LcrF-DNA binding assay as well as in a secondary whole cell assay (type III secretion system dependent Y. pseudotuberculosis cytotoxicity assay). The inhibitors exhibited no measurable antibacterial activity in vitro, confirming that they do not target bacterial growth. These results demonstrate that N-hydroxy-benzimidazole inhibitors, exemplified by 14, 22, and 36, are effective antivirulence agents and have the potential to prevent infections caused by Yersinia spp.