(E)-3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)prop-2-en-1-one
• 英文别名: (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one；(E)-3-(4-dimethylaminophenyl)-1-(2-pyridyl)prop-2-en-1-one；(E)-3-[4-(dimethylamino)phenyl]-1-pyridin-2-ylprop-2-en-1-one
• 化学式: C₁₆H₁₆N₂O
• 分子量: 252.316
• InChiKey: RQOIXZNDFXKOQY-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)prop-2-en-1-one 在 二苯硫醚 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以51%的产率得到3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)propan-1-one
  参考文献：
  名称：

  Tuning Reactivity of Diphenylpropynone Derivatives with Metal-Associated Amyloid-β Species via Structural Modifications

  摘要：

  A diphenylpropynone derivative, DPP2, has been recently demonstrated to target metal-associated amyloid-beta (metal-A beta) species implicated in Alzheimer's disease (AD). DPP2 was shown to interact with metal-A beta species and subsequently control A beta aggregation (reactivity) in vitro; however, its cytotoxicity has limited further biological applications. In order to improve reactivity toward A beta species and lower cytotoxicity, along with gaining an understanding of a structure-reactivity-cytotoxicity relationship, we designed, prepared, and characterized a series of small molecules (C1/C2, P1/P2, and PA1/PA2) as structurally modified DPP2 analogues. A similar metal binding site to that of DPP2 was contained in these compounds while their structures were varied to afford different interactions and reactivities with metal ions, A beta species, and metal-A beta species. Distinct reactivities of our chemical family toward in vitro A beta aggregation in the absence and presence of metal ions were observed. Among our chemical series, the compound (C2) with a relatively rigid backbone and a dimethylamino group was observed to noticeably regulate both metal-free and metal-mediated A beta aggregation to different extents. Using our compounds, cell viability was significantly improved, compared to that with DPP2. Lastly, modifications on the DPP framework maintained the structural properties for potential blood-brain barrier (BBB) permeability. Overall, our studies demonstrated that structural variations adjacent to the metal binding site of DPP2 could govern different metal binding properties, interactions with A beta and metal-A beta species, reactivity toward metal-free and metal-induced A beta aggregation, and cytotoxicity of the compounds, establishing a structure-reactivity-cytotoxicity relationship. This information could help gain insight into structural optimization for developing nontoxic chemical reagents toward targeting metal-A beta species and modulating their reactivity in biological systems.

  DOI：

  10.1021/ic400851w
• 作为产物：
  描述：

  2-氰基吡啶 在 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 水 为溶剂， 反应 3.08h， 生成 (E)-3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)prop-2-en-1-one
  参考文献：
  名称：

  Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones

  摘要：

  合成了二十种查尔酮衍生物，发现它们能够结合Cu²⁺和Zn^{2+>离子，调节Aβ聚集物的解离，并抑制乙酰胆碱酯酶活性。这些查尔酮显示出在阿尔茨海默病探针和/或治疗药物开发方面的潜力。}

  DOI：

  10.1039/c5ob01478f

文献信息

• Synthesis, Structural characterization, thermal, molecular modeling and biological studies of chalcone and Cr(III), Mn(II), Cu(II) Zn(II) and Cd(II) chelates
  作者：Tarek A. Fayed、M. Gaber、Marwa N. El-Nahass、H.A. Diab、Mohammed M. El-Gamil

  DOI：10.1016/j.molstruc.2020.128742

  日期：2020.12

  Abstract A number of new Cr(III), Mn(II), Cu(II) Zn(II) and Cd(II) chelates of (E)-3-(4-(dimethyl-amino)phenyl)-1-(pyridin-2-yl)prop-2-en-1-one were synthesized. The structures were elucidated by elemental and thermal analysis as well as spectral techniques (mass, IR, and electronic spectra) and magnetic measurements. The IR data suggested that the investigated chalcone acted as a bidentate ligand

  摘要 (E)-3-(4-(二甲基-氨基)苯基)-1-(E)-3-(4-(二甲基-氨基)苯基)-( pyridin-2-yl)prop-2-en-1-one 合成。通过元素和热分析以及光谱技术（质量、红外和电子光谱）和磁性测量阐明了结构。红外数据表明，所研究的查耳酮分别通过 CO 和 CN 基团的 O 和 N 原子充当双齿配体。光谱加磁数据揭示了所有螯合物的八面体结构的形成，而 Cu(II) 螯合物具有方形平面几何形状。已经评估了热分解阶段的动力学和热力学参数。已进行分子轨道计算以确认分离化合物的几何形状。查耳酮及其金属螯合物的体外抗微生物活性已针对某些细菌菌株进行。数据表明所有金属螯合物都表现出比游离查耳酮更高的活性。针对 MCF7 细胞评估了上述金属螯合物的抗癌活性。这些化合物对测试的细胞系表现出中等和微弱的活性。结果与实验数据相关。
• Design, Docking, and Synthesis of Some New Pyrazoline and Pyranopyrazole Derivatives as Anti-inflammatory Agents
  作者：Magda M. F. Ismail、Nagy M. Khalifa、Hoda H. Fahmy、Eman S. Nossier、Mohamed M. Abdulla

  DOI：10.1002/jhet.1757

  日期：2014.3

  Design and synthesis of some novel pyrazoline and pyranopyrazole derivatives as potential anti‐inflammatory agents are described. Most of the compounds were tested for their anti‐inflammatory (in vitro and in vivo) and ulcerogenic activities. In all tested compounds, it was found that pyrazolines, 2a, and pyrazolopyrano[2,3‐d]pyrimidine 9 are the potent anti‐inflammatory and selective cyclooxygenase‐2

  描述和设计了一些新型的吡唑啉和吡喃并吡唑衍生物作为潜在的抗炎药。测试了大多数化合物的抗炎作用（体外和体内）和致溃疡活性。在所有测试的化合物中，发现吡唑啉2a和吡唑并吡喃并[2,3- d ]嘧啶9是有效的抗炎和选择性环氧合酶2（COX-2）抑制剂。所有化合物主要处于安全水平。对2a和9的对接研究表明，它与COX-2酶的活性位点（如选择性COX-2抑制剂SC-558）的结合亲和力更高。
• A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe
  作者：Jenna M. Len、Noor Hussein、Saloni Malla、Kyle Mcintosh、Rahul Patidar、Manivannan Elangovan、Karthikeyan Chandrabose、N. S. Hari Narayana Moorthy、Manoj Pandey、Dayanidhi Raman、Piyush Trivedi、Amit K. Tiwari

  DOI：10.3390/molecules26144214

  日期：——

  In this study, we designed, synthesized and evaluated, in vitro, novel chalcone analogs containing dialkylamino pharmacophores in the cervical cancer cell line, OV2008. The compound, DML6 was selective and significantly decreased the proliferation of OV2008 and HeLa cells in sub-micromolar concentrations, compared to prostate, lung, colon, breast or human embryonic kidney cell line (HEK293). DML6,

  在这项研究中，我们在体外设计、合成并评估了宫颈癌细胞系 OV2008 中含有二烷基氨基药效团的新型查耳酮类似物。与前列腺、肺、结肠、乳腺或人胚肾细胞系 (HEK293) 相比，该化合物DML6具有选择性，在亚微摩尔浓度下可显着降低 OV2008 和 HeLa 细胞的增殖。 5 μM 的 DML6 使 OV2008 细胞停滞在 G2 期。此外，与用载体孵育的 OV2008 细胞相比，5 μM的 DML6增加了活性氧水平，并诱导线粒体膜电位崩溃。与细胞相比，5 μM 的DML6通过显着 (1) 增加促凋亡蛋白 Bak 和 Bax 的水平，以及 (2) 降低抗凋亡蛋白 Bcl-2 的水平来诱导内在凋亡与载体一起孵化。此外，5 和 20 μM 的 DML6 诱导 caspase-9 裂解，随后裂解刽子手 caspase、caspase-3 和 caspase-7，从而导致 OV2008 细胞死亡。
• Simple, Rapid and Reliable Preparation of [11C]-(+)-a-DTBZ of High Quality for Routine Applications
  作者：Jinming Zhang、Xiaojun Zhang、Yungang Li、Jiahe Tian

  DOI：10.3390/molecules17066697

  日期：——

  [11C]-(+)-a-DTBZ has been used as a marker of dopaminergic terminal densities in human striatum and expressed in islet beta cells in the pancreas. We aimed to establish a fully automated and simple procedure for the synthesis of [11C]-(+)-a-DTBZ for routine applications. [11C]-(+)-a-DTBZ was synthesized from a 9-hydroxy precursor in acetone and potassium hydroxide with [11C]-methyl triflate and was purified by solid phase extraction using a Vac tC-18 cartridge. Radiochemical yields based on [11C]-methyl triflate (corrected for decay) were 82.3% ± 3.6%, with a specific radioactivity of 60 GBq/mmol. Time elapsed was less than 20 min from end of bombardment to release of the product for quality control.

  [11C]-(+)-a-DTBZ已被用作人类纹状体中多巴胺能终端密度的标记物，并在胰腺的胰岛β细胞中表达。我们旨在建立一个完全自动化和简单的程序，以合成[11C]-(+)-a-DTBZ，以便进行常规应用。[11C]-(+)-a-DTBZ是从一种9-羟基前体在丙酮和氢氧化钾的条件下与[11C]-甲基三氟甲磺酸酯合成的，并通过使用Vac tC-18柱的固相提取进行纯化。基于[11C]-甲基三氟甲磺酸酯（已校正衰减）的放射化学产率为82.3% ± 3.6%，具有60 GBq/mmol的比放射活性。从轰击结束到产品释放进行质量控制的时间少于20分钟。
• Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease
  作者：Xiao‐Qin Wang、Lu‐Yi Zhou、Ren‐Xian Tan、Guo‐Peng Liang、Si‐Xian Fang、Wei Li、Mei Xie、Yu‐Hao Wen、Jia‐Qiang Wu、Yi‐Ping Chen

  DOI：10.1002/cbdv.202100341

  日期：2021.11

  Fifteen chalcone derivatives 3a–3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ1-42 aggregation effectively ranged from 45.9–94.5 % at 20 μM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-

  合成了15 种查耳酮衍生物3a – 3o，并作为抗阿尔茨海默病的多功能药物进行了评估。体外研究表明，这些化合物在 20 μM 时有效抑制自诱导 Aβ 1-42聚集的范围为 45.9–94.5 %，并充当潜在的抗氧化剂。总结了它们的构效关系。特别是，( 2E )-3-[4-(二甲基氨基)苯基]-1-(吡啶-2-基)丙-2-烯-1-酮( 3g )在20℃时表现出94.5%的优异抑制活性μM，在20 μM浓度下可分解自诱导的Aβ 1-42聚集原纤维，比例为57.1 %。另外，复方3g对Cu 2+表现出良好的螯合能力，能有效抑制和解聚Cu 2+诱导的Aβ聚集。此外，化合物3g具有低细胞毒性，显着逆转 Aβ 1-42诱导的 SH-SY5Y 细胞损伤。更重要的是，化合物3g显着改善了东莨菪碱引起的小鼠记忆障碍。总之，所有结果表明化合物3g是一种潜在的 AD 治疗多功能药物。