(E)-3-(3,4-dimethoxyphenyl)-1-(3-nitrophenyl)prop-2-en-1-one | 75573-20-5

• 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-(3,4-dimethoxyphenyl)-1-(3-nitrophenyl)prop-2-en-1-one
• CAS: 75573-20-5
• 化学式: C₁₇H₁₅NO₅
• 分子量: 313.31
• InChiKey: FDKQLSPNBYBNKV-SOFGYWHQSA-N

物化性质

• 沸点：
  491.7±45.0 °C(Predicted)
• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 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：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4-dimethoxyphenyl)-1-(3-nitrophenyl)prop-2-en-1-one 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 N,N'-二环己基碳二亚胺 、 (+)-二异松蒎基氯硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 乙酸乙酯 为溶剂， -45.0~150.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 (R)-1-(3-((tert-butoxycarbonyl)amino)phenyl)-3-(3,4-dimethoxyphenyl)propyl (S)-1-(2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxylate
  参考文献：
  名称：

  靶向共价抑制疟原虫FK506结合蛋白35

  摘要：

  FK506结合蛋白35，FKBP35，已被认为是必需的疟疾酶。雷帕霉素和FK506在培养的寄生虫中表现出抗疟原虫活性。然而，由于FKBP的结合口袋的高度保守的性质和这些药物的免疫抑制特性，需要选择性地抑制FKBP35并且缺乏不良副作用的化合物。与人FKBP相比，FKBP35在雷帕霉素结合口袋附近包含一个半胱氨酸C106，为开发靶向疟原虫FKBP35的共价抑制剂提供了机会。在这里，我们合成了FKBP35的抑制剂，表明它们在模型细胞环境中直接结合FKBP35，选择性地共价修饰C106，并在血阶段培养的寄生虫中表现出抗疟原虫活性。

  DOI：

  10.1021/acsmedchemlett.0c00272
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 、 间硝基苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以56%的产率得到(E)-3-(3,4-dimethoxyphenyl)-1-(3-nitrophenyl)prop-2-en-1-one
  参考文献：
  名称：

  靶向共价抑制疟原虫FK506结合蛋白35

  摘要：

  FK506结合蛋白35，FKBP35，已被认为是必需的疟疾酶。雷帕霉素和FK506在培养的寄生虫中表现出抗疟原虫活性。然而，由于FKBP的结合口袋的高度保守的性质和这些药物的免疫抑制特性，需要选择性地抑制FKBP35并且缺乏不良副作用的化合物。与人FKBP相比，FKBP35在雷帕霉素结合口袋附近包含一个半胱氨酸C106，为开发靶向疟原虫FKBP35的共价抑制剂提供了机会。在这里，我们合成了FKBP35的抑制剂，表明它们在模型细胞环境中直接结合FKBP35，选择性地共价修饰C106，并在血阶段培养的寄生虫中表现出抗疟原虫活性。

  DOI：

  10.1021/acsmedchemlett.0c00272

文献信息

• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。
• Rapafucin derivative compounds and methods of use thereof
  申请人：The Johns Hopkins University

  公开号：US11066416B2

  公开（公告）日：2021-07-20

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受天然产物 FK506 和雷帕霉素的免疫嗜蛋白配体家族启发的大环化合物。由含有 FK506 和雷帕霉素结合结构域的大环化合物组成的雷帕霉素库，作为开发用于治疗疾病的药物的新线索，具有巨大的潜力。
• Synthesis and evaluation of new chalcones, derived pyrazoline and cyclohexenone derivatives as potent antimicrobial, antitubercular and antileishmanial agents
  作者：Vikramdeep Monga、Kamya Goyal、Mario Steindel、Manav Malhotra、Dhanji P. Rajani、Smita D. Rajani

  DOI：10.1007/s00044-013-0803-1

  日期：2014.4

  A series of chalcones (1-8) were prepared by Claisen-Schmidt condensation of 3-nitroacetophenone with various aldehydes. These chalcones on cyclization with hydrazine hydrate in the presence of glacial acetic acid, hydrazine hydrate in absolute ethanol and ethyl acetoacetate in the presence of barium hydroxide gave corresponding N-acetyl pyrazolines (9-16), N-unsubstituted pyrazolines (17-19) and cyclohexenone derivatives (20-22). All the synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity by using broth microdilution method, and many compounds showed promising activity against various tested bacteria and fungi. Among various tested compounds, 16 and 19 exhibited strongest activities against Streptococcus pyogenes and Pseudomonas aeruginosa; both have MIC value of 25 mu g/mL, which is fourfold greater than the standard drug. Many compounds showed good activity against Candida albican. Analogs 11, 12, 15-17 and 19 displayed two- to fivefold greater activity against C. albican as compared to the standard drug. Results of antitubercular evaluation revealed that compounds 4 and 19 displayed strong antimycobacterial activity against H(37)Rv having MIC of 25 and 62.5 mu g/mL, respectively. All analogs were found to be inactive against Leishmania braziliensis except analogs 4 and 5 which exhibited strong leishmanicidal activity against Leishmania promastigotes with IC50 values of 9.3 and 8.9 mu g/mL, respectively.
• Synthesis, antimycobacterial activity evaluation, and QSAR studies of chalcone derivatives
  作者：P.M. Sivakumar、S. Prabu Seenivasan、Vanaja Kumar、Mukesh Doble

  DOI：10.1016/j.bmcl.2006.12.112

  日期：2007.3

  In order to develop relatively small molecules as antimycobacterial agents, twenty-five chalcones were synthesized, their activity was evaluated, and quantitative structure-activity relationship (QSAR) was developed. The synthesis was based on the Claisen-Schimdt scheme and the resultant compounds were tested for antitubercular activity by luciferase reporter phage (LRP) assay. Compound C-24 was found to be the most active (similar to 99%) in this series based on the percentage reduction in Relative Light Units at both 50 and 100 mu g/ml levels, followed by compound C-21. Four compounds at the 50 mu g/ml and eight compounds at the 100 mu g/ml showed activity above 90% level. QSAR model was developed between activity and spatial, topological, and ADME descriptors for the 50 mu g/ml data. The statistical measures such as r, r(2), q(2), and F values obtained for the training set were in acceptable range and hence this relationship was used for the test set. The predictive ability of the model is satisfactory (q(2) = 0.56) and it can be used for designing similar group of compounds. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and activity of bivalent FKBP12 ligands for the regulated dimerization of proteins
  作者：Terence Keenan、David R. Yaeger、Nancy L. Courage、Carl T. Rollins、Mary Ellen Pavone、Victor M. Rivera、Wu Yang、Tao Guo、Jane F. Amara、Tim Clackson、Michael Gilman、Dennis A. Holt

  DOI：10.1016/s0968-0896(98)00125-4

  日期：1998.8

  The total synthesis and in vitro activities of a series of chemical inducers of dimerization (CIDs) is described. The use of small-molecule CIDs to control the dimerization of engineered FKBP12-containing fusion proteins has been demonstrated to have broad utility in biological research as well as potential medical applications in gene and cell therapies. The facility and flexibility of preparation make this new class of wholly synthetic compounds exceptionally versatile tools for the study of intracellular signaling events mediated by protein-protein interactions or protein localization. While some congeners possess potency comparable to or better than the first generation natural product-derived CID, FK1012, structure-activity relationships are complex and underscore the need for application-specific compound optimizations. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.