(E)-3-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one | 53744-30-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one
• 英文别名: BG0401；3-(4-Chlorophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one
• CAS: 53744-30-2
• 化学式: C₁₇H₁₅ClO₃
• 分子量: 302.757
• InChiKey: VJAYGIKWBKGYJF-WEVVVXLNSA-N

物化性质

• 沸点：
  461.6±45.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one 在 三溴化硼 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-(1,5-bis(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)benzene-1,2-diol
  参考文献：
  名称：

  通过蛋白激酶 Czeta (PKCz) 的变构抑制来设计和合成新型 1,3,5-三苯基吡唑啉作为潜在的抗炎剂†

  摘要：

  人们对蛋白激酶 Czeta (PKC z) 在 NF-κB 激活中的重要作用以及 PKC z 抑制剂作为抗炎剂的潜在用途有了更多的了解。我们之前报道了一系列 1,3,5-三取代吡唑啉作为 PKCδ 的有效和选择性变构抑制剂；在该系列化合物中，5-苯基处的酚 OH 对于与 PKC z PIF 口袋的结合至关重要。在本研究中，我们令人惊讶地发现，用卤素取代它并同时将 OH 移至 3-苯基仍然会产生活性化合物。本文提出了此类化合物的扩展，具有新的重点库，其中 5-苯基处的酚羟基（据报道是活性的不可替代特征）被移至 3-苯基并被卤素取代。这组新化合物保持了相同水平的针对 PKCζ 的效力和针对 PKC 同工型的选择性，但针对 PIF 口袋突变体 PKCζ[Val297Leu] 的效力降低。值得注意的是，关键功能组的重新定位导致细胞效力显着增强。最有效的新型 PKC z 抑制剂之一2h能够抑制 RAW

  DOI：

  10.1039/c8md00100f
• 作为产物：
  描述：

  (2E)-1-(3,4-dimethoxyphenyl)-3-(2,3,4-trimethoxyphenyl)prop-2-en-1-one 在 sodium hydroxide 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 0.33h， 生成 (E)-3-(4-chlorophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  The synthesis of indanones related to combretastatin A-4 via microwave-assisted Nazarov cyclization of chalcones

  摘要：

  A fast and efficient microwave-assisted synthesis of combretastatin A-4-like indationes has been developed. Microwave irradiation provides a useful alternative to traditional heating techniques to promote the TFA-catalyzed Nazarov cyclization of chalcones. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.12.110

文献信息

• A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency
  作者：Bin Wang、Li-Ren Wang、Lu-Lu Liu、Wei Wang、Ruo-Jun Man、Da-Jun Zheng、Yu-Shan Deng、Yu-Shun Yang、Chen Xu、Hai-Liang Zhu

  DOI：10.1016/j.bioorg.2020.104585

  日期：2021.3

  In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker for CA-4 modification for the first time. Among them, the hit compound D8 showed potential on inhibiting the growth of several cancer cell lines (IC50

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。
• Effect on Acetylcholinesterase and Anti-oxidant Activity of Synthetic Chalcones having a Good Predicted Pharmacokinetic Profile
  作者：Renata P. Sakata、Micheli Figueiro、Daniel F. Kawano、Wanda P. Almeida

  DOI：10.2174/1573406413666170525125730

  日期：2017.10.17

  Background: Acetylcholinesterase (AChE) is an important target in the development of drug to treat Alzheimer's disease (AD). In this work, we investigated the effect of twenty-two synthesized chalcones on AChE activity. Objective: This work is aimed to synthesize and evaluate the effect of chalcones on the AChE activity, as well as anti-oxidant activity and predict their pharmacokinetic profile. Method: Chalcones were synthesized through a Claisen-Schmidt condensation and their inhibitory effect on the AChE was evaluated by the Elmann's colorimetric method. To determine the anti-oxidant activity the DPPH radical scavenging method was chosen. Results: We found that all chalcones inhibit this activity, with IC50 values ranging from 0.008 to 4.8 µM. We selected the most active compound 19 with an IC50 value of 0.008 µM for a kinetic study demonstrating a competitive inhibition mode. Molecular docking simulations showed a good interaction between 19 and the active site of AChE. Considering the prediction of pharmacokinetic parameters being a useful tool for selecting potential drug candidates, our study results suggest that the majority of chalcones, including the most active one, have a promising pharmacokinetic profile and blood-brain barrier permeability. The involvement of reactive oxygen species (ROS) in AD-related events has encouraged us to evaluate these chalcones as radical scavengers. Conclusion: We have found that compound 19 is a potent AChE inhibitor, and based on kinetic studies, it acts as a competitive inhibitor.

  背景：乙酰胆碱酯酶（AChE）是开发治疗阿尔茨海默病（AD）药物的重要靶点。本研究中，我们探讨了22种合成的查尔酮对AChE活性的影响。 目标：本工作的目的是合成并评估查尔酮对AChE活性的影响，以及其抗氧化活性并预测其药代动力学特征。 方法：通过克莱森-施密特缩合合成查尔酮，并采用Elmann比色法评估其对AChE的抑制作用。为了确定抗氧化活性，选择了DPPH自由基清除法。 结果：我们发现所有查尔酮均抑制该活性，IC50值范围为0.008至4.8 µM。我们选择了活性最强的化合物19，其IC50值为0.008 µM，进行动力学研究，结果表明其呈现竞争性抑制模式。分子对接模拟显示化合物19与AChE的活性位点之间有良好的相互作用。考虑到药代动力学参数的预测是选择潜在药物候选物的有用工具，我们的研究结果表明，大多数查尔酮，包括活性最强的，具有良好的药代动力学特征和血脑屏障渗透性。反应性氧种（ROS）在AD相关事件中的参与促使我们评估这些查尔酮作为自由基清除剂的潜力。 结论：我们发现化合物19是一种有效的AChE抑制剂，基于动力学研究，它作为竞争性抑制剂发挥作用。
• 찰콘 유도체를 포함하는 신장 보호용 조성물
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY 한국과학기술연구원(319980077518) BRN ▼209-82-03522

  公开号：KR20190050074A

  公开（公告）日：2019-05-10

  본 명세서는 찰콘 유도체를 포함하는 신장 보호용 조성물 또는 신장질환 개선용 조성물에 관한 것으로서, 본 명세서에 의한 화합물을 이용할 경우 약물 등에 의한 신독성으로부터 신장을 보호할 수 있어, 약물과 관련된 신장질환의 효과적 개선을 도모할 수 있으므로, 본 명세서를 활용하여 환자 치료 및 복지 분야에 있어서 큰 기여를 도모할 수 있을 것이다.

  该规范涉及包含钙调素诱导体的肾脏保护配方或肾脏疾病改善配方，通过使用本规范中的化合物，可以保护肾脏免受药物等的肾毒性，从而促进与药物相关的肾脏疾病的有效改善，因此利用本规范可以在患者治疗和福利领域做出重大贡献。
• Benzannulation of 3-Substituted Pyrroles to Indoles
  作者：Alan R. Katritzky、Stephane Ledoux、Satheesh K. Nair

  DOI：10.1021/jo026853m

  日期：2003.7.1

  In a new general indole synthesis, the anion derived from benzotriazolyl derivative 5b underwent regioselective 1,4-addition to various alpha,beta-unsaturated ketones; subsequent acid-catalyzed cyclization formed the corresponding indoles 1a-f.

  在新的一般吲哚合成中，衍生自苯并三唑基衍生物5b的阴离子在各种α，β-不饱和酮上进行了区域选择性的1,4-加成。随后酸催化的环化反应形成相应的吲哚1a-f。
• Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein
  作者：Kapil Juvale、Veronika F.S. Pape、Michael Wiese

  DOI：10.1016/j.bmc.2011.10.074

  日期：2012.1

  Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the current study was to investigate different multi-substituted chalcones for their BCRP inhibition. We synthesized chalcones and benzochalcones with different substituents (viz. OH, OCH3, Cl) on ring A and B of the chalcone structure. All synthesized compounds were tested by Hoechst 33342 accumulation assay to determine inhibitory activity in MCF-7 MX and MDCK cells expressing BCRP. The compounds were also screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity in the calcein AM accumulation assay and were found to be selective towards inhibition of BCRP. Substituents at position 20 and 40 on chalcone ring A were found to be essential for activity; additionally there was a great influence of substituents on ring B. Presence of 3,4-dimethoxy substitution on ring B was found to be optimal, while presence of 2- and 4-chloro substitution also showed a positive effect on BCRP inhibition. (C) 2011 Elsevier Ltd. All rights reserved.