[(E)-3-(dimethylamino)-2-(4-fluorophenyl)prop-2-enylidene]-dimethylazanium;perchlorate | 252950-06-4

• 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-(dimethylamino)-2-(4-fluorophenyl)prop-2-enylidene]-dimethylazanium;perchlorate
• CAS: 252950-06-4
• 化学式: C₁₃H₁₈FN₂*ClO₄
• 分子量: 320.748
• InChiKey: RUQQPHJBUHIBQX-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.68
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  80.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(E)-3-(dimethylamino)-2-(4-fluorophenyl)prop-2-enylidene]-dimethylazanium;perchlorate 在 吡啶 、 sodium methylate 作用下， 反应 24.0h， 以31.5%的产率得到1-methyl-3-(4-fluorophenyl)pyrrole
  参考文献：
  名称：

  Structure–activity relationships in the inhibition of monoamine oxidase B by 1-methyl-3-phenylpyrroles

  摘要：

  Methyl-3-phenyl-3-pyrrolines are structural analogues of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and like MPTP are selective substrates of monoamine oxidase B (MAO-B). As part of an ongoing investigation into the substrate properties of various 1-methyl-3-phenyl-3-pyrrolinyl derivatives, it is shown in the present study that their respective MAO-B catalyzed oxidation products act as reversible competitive inhibitors of the enzyme. The most potent inhibitor among the oxidation products considered was 1-methyl-3-(4-trifluoromethylphenyl)pyrrole with an enzyme-inhibitor dissociation constant (K-i value) of 1.30 mu M. The least potent inhibitor was found to be 1-methyl-3-phenylpyrrole with a K-i value of 118 mu M. The results of an SAR study established that the potency of MAO-B inhibition by the 1-methyl-3-phenylpyrrolyl derivatives examined here is dependent on the Taft steric parameter (E-s) and Swain-Lupton electronic constant (F) of the substituents attached to C-4 of the phenyl ring. Electron-withdrawing substituents with a large degree of steric bulkiness appear to enhance inhibition potency. Potency was also found to vary with the substituents at C-3, again with E-s and F being the principal substituent descriptors. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.059
• 作为产物：
  描述：

  N,N-二甲基甲酰胺 、 4-氟苯乙酸 在 三氯氧磷 作用下， 以67.8%的产率得到[(E)-3-(dimethylamino)-2-(4-fluorophenyl)prop-2-enylidene]-dimethylazanium;perchlorate
  参考文献：
  名称：

  Structure–activity relationships in the inhibition of monoamine oxidase B by 1-methyl-3-phenylpyrroles

  摘要：

  Methyl-3-phenyl-3-pyrrolines are structural analogues of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and like MPTP are selective substrates of monoamine oxidase B (MAO-B). As part of an ongoing investigation into the substrate properties of various 1-methyl-3-phenyl-3-pyrrolinyl derivatives, it is shown in the present study that their respective MAO-B catalyzed oxidation products act as reversible competitive inhibitors of the enzyme. The most potent inhibitor among the oxidation products considered was 1-methyl-3-(4-trifluoromethylphenyl)pyrrole with an enzyme-inhibitor dissociation constant (K-i value) of 1.30 mu M. The least potent inhibitor was found to be 1-methyl-3-phenylpyrrole with a K-i value of 118 mu M. The results of an SAR study established that the potency of MAO-B inhibition by the 1-methyl-3-phenylpyrrolyl derivatives examined here is dependent on the Taft steric parameter (E-s) and Swain-Lupton electronic constant (F) of the substituents attached to C-4 of the phenyl ring. Electron-withdrawing substituents with a large degree of steric bulkiness appear to enhance inhibition potency. Potency was also found to vary with the substituents at C-3, again with E-s and F being the principal substituent descriptors. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.059

文献信息

• Inhibitors of glycogen synthase kinase 3
  申请人：——

  公开号：US20020156087A1

  公开（公告）日：2002-10-24

  New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

  提供新的基于嘧啶或吡啶的化合物、组合物以及抑制糖原合酶激酶（GSK3）活性的方法和治疗GSK3介导的体内疾病的方法。发明的方法、化合物和组合物可以单独使用，或者与其他药理活性物质结合使用，在治疗由GSK3活性介导的疾病中，如糖尿病、阿尔茨海默病和其他神经退行性疾病、肥胖、动脉粥样硬化性心血管疾病、原发性高血压、多囊卵巢综合征、X综合征、缺血、创伤性脑损伤、双相情感障碍、免疫缺陷或癌症。
• Highly Fluorescent Pyrido[2,3-<i>b</i> ]indolizine-10-Carbonitriles through Pseudo Three-Component Reactions of <i>N</i> -(Cyanomethyl)pyridinium Salts
  作者：Ekaterina A. Sokolova、Alexey A. Festa、Nikita E. Golantsov、Natalia S. Lukonina、Ilya N. Ioffe、Alexey V. Varlamov、Leonid G. Voskressensky

  DOI：10.1002/ejoc.201900995

  日期：2019.10.31

  A novel class of effective fluorophores, incorporating the pyrido[2,3‐b]indolizine scaffold, has been discovered. The synthesis of pyridoindolizines involves one synthetic step from readily available starting materials.

  已发现一类新型的有效荧光团，其中掺入了吡啶并[2,3- b ]吲哚嗪骨架。吡啶并吲哚并恶嗪的合成涉及从容易获得的起始原料开始的一个合成步骤。
• Synthesis and in vitro anticoagulant activity of 3-(1H-imidazo[4,5-c]pyridin-2-yl)-1,5-diarylpyridin-2(1H)-one derivatives
  作者：Jiabin Yang、Guoqiang Su、Yu Ren、Yang Chen

  DOI：10.1007/s11164-015-1927-3

  日期：2015.11

  A series of 3-(1 H -imidazo[4,5- c ]pyridin-2-yl)-1,5-diarylpyridin-2(1 H )-one derivatives were designed and synthesized as potential anticoagulant agents. The 1,5-diarylpyridin-2(1 H )-ones, key intermediates of these anticoagulants, were synthesized by a simple reaction of 2-aryl vinamidinium salts with ethyl 3-oxo-3-(arylamino)propanoate derivatives. The prothrombin time in canine blood showed

  设计并合成了一系列3-（1 H- 咪唑并[4,5- c ]吡啶-2-基）-1,5-二芳基吡啶-2（1 H ）-一衍生物，作为潜在的抗凝剂。这些抗凝血剂的关键中间体1,5-二芳基吡啶2-2 （1 H ）-是通过2-芳基乙烯基盐与3-氧代-3-（芳基氨基）丙酸乙酯衍生物的简单反应合成的。犬血中凝血酶原时间表明，其中的氨基和羟甲基衍生物具有明显的抗凝能力（PT = 17.07 s）。
• Synthesis and biological evaluation of some novel N-arylpyrazole derivatives as cytotoxic agents
  作者：Shenghui Li、Shengjie Xu、Shan Ding、Jinchao Zhang、Shuxiang Wang、Xiaoliu Li

  DOI：10.1007/s11164-013-1051-1

  日期：2014.4

  A series of novel N-arylpyrazole derivatives, 5a–5i, were achieved from substituted phenylacetic acid via Vilsmeier–Haack reaction, hydrolysis, condensation, and aromatic substitution reaction. Their chemical structures were confirmed by 1H NMR, 13C NMR, FTIR, HRMS, and elemental analysis. The newly synthesized compounds were tested for their in vitro cytotoxic activity against Bel-7402, KB, HL-60, and BGC-823 cell lines and found to possess moderate activity.

  通过 Vilsmeier-Haack 反应、水解、缩合和芳香取代反应，从取代的苯乙酸中获得了一系列新型 N-芳基吡唑衍生物 5a-5i。通过 1H NMR、13C NMR、FTIR、HRMS 和元素分析确认了它们的化学结构。新合成的化合物对 Bel-7402、KB、HL-60 和 BGC-823 细胞系进行了体外细胞毒活性测试，结果发现它们具有中等程度的活性。
• Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives
  作者：Shenghui Li、Shengjie Xu、Yonghe Tang、Shan Ding、Jinchao Zhang、Shuxiang Wang、Guoqiang Zhou、Chuanqi Zhou、Xiaoliu Li

  DOI：10.1016/j.bmcl.2013.12.014

  日期：2014.1

  series of 4-pyrazolyl-1,8-naphthalimide derivatives have been designed and facilely synthesized. For anticancer activity in vitro, most of the compounds were found to be more toxic against human mammary cancer cells (MCF-7) than human cervical carcinoma cells (Hela) and human lung cancer cells (A549). Compounds 4i, 4h, 4b and 4a showed improved cytotoxic activity against MCF-7 cells over amonafide, in

  已经设计并容易地合成了一系列新颖的4-吡唑基-1，8-萘二甲酰亚胺衍生物。对于体外抗癌活性，发现大多数化合物对人乳腺癌细胞（MCF-7）的毒性比人宫颈癌细胞（Hela）和人肺癌细胞（A549）高。化合物4i，4h，4b和4a与阿莫那肽相比对MCF-7细胞表现出改善的细胞毒活性，尤其是化合物4i和4h，其对MCF-7细胞系的IC 50值分别为0.51μM和0.79μM 。4i的DNA结合特性通过紫外可见光谱，荧光和圆二色性（CD）光谱学和热变性进行了研究。结果表明，作为DNA嵌入剂的化合物4i显示出与CT-DNA的中等结合亲和力。