(benzo[d]oxazol-2-yl)methyltriphenylphosphonium chloride | 139549-58-9

• 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: (benzo[d]oxazol-2-yl)methyltriphenylphosphonium chloride
• 英文别名: [(1,3-Benzoxazol-2-yl)methyl](triphenyl)phosphanium chloride；1,3-benzoxazol-2-ylmethyl(triphenyl)phosphanium;chloride
• CAS: 139549-58-9
• 化学式: C₂₆H₂₁NOP*Cl
• 分子量: 429.886
• InChiKey: BWHMPPWGQMPESF-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (benzo[d]oxazol-2-yl)methyltriphenylphosphonium chloride 在 potassium tert-butylate 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 0.5h， 生成 (E)-2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole
  参考文献：
  名称：

  Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes

  摘要：

  The formation of proteinaceous aggregates is a pathognomonic hallmark of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. To date, the final diagnostic for these diseases can only be achieved by immunostaining of post-mortem brain tissues with the commonly used congo red and Thioflavin T/S amyloid-dyes. The interest in developing amyloid-avid radioprobes to be used for protein aggregates imaging by positron emission tomography has grown substantialy, due to the promise in assisting diagnosis of these disorders. To this purpose, the present work describes the synthesis and characterization of four novel fluorinated styryl benzazole derivatives 1-4 by means of the Wittig reaction, as well as their in vitro evaluation as amyloid-probing agents. All compounds were obtained as mixtures of geometric E and Z isomers, with the preferable formation of the E isomer. Photoisomerization reactions allowed for the maximization of the minor Z isomers. The authentic 1-4E/Z isomers were isolated after purification by column chromatography under dark conditions. Profiting from the fluorescence properties of the different geometric isomers of 1-4, their binding affinities towards amyloid fibrils of insulin, alpha-synuclein and beta-amyloid peptide were also measured. These compounds share similarities with Thioflavin T, interacting specifically with fibrillary species with a red-shift in the excitation wavelengths along with an increase in the fluorescence emission intensity. Apparent binding constants were determined and ranged between 1.22 and 23.96 mu M-1. The present data suggest that the novel fluorinated styryl benzazole derivatives may prove useful for the design of F-18-labeled amyloid radioprobes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.065
• 作为产物：
  描述：

  2-氨基苯酚 在 磷酸 作用下， 以 甲苯 为溶剂， 生成 (benzo[d]oxazol-2-yl)methyltriphenylphosphonium chloride
  参考文献：
  名称：

  Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes

  摘要：

  The formation of proteinaceous aggregates is a pathognomonic hallmark of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. To date, the final diagnostic for these diseases can only be achieved by immunostaining of post-mortem brain tissues with the commonly used congo red and Thioflavin T/S amyloid-dyes. The interest in developing amyloid-avid radioprobes to be used for protein aggregates imaging by positron emission tomography has grown substantialy, due to the promise in assisting diagnosis of these disorders. To this purpose, the present work describes the synthesis and characterization of four novel fluorinated styryl benzazole derivatives 1-4 by means of the Wittig reaction, as well as their in vitro evaluation as amyloid-probing agents. All compounds were obtained as mixtures of geometric E and Z isomers, with the preferable formation of the E isomer. Photoisomerization reactions allowed for the maximization of the minor Z isomers. The authentic 1-4E/Z isomers were isolated after purification by column chromatography under dark conditions. Profiting from the fluorescence properties of the different geometric isomers of 1-4, their binding affinities towards amyloid fibrils of insulin, alpha-synuclein and beta-amyloid peptide were also measured. These compounds share similarities with Thioflavin T, interacting specifically with fibrillary species with a red-shift in the excitation wavelengths along with an increase in the fluorescence emission intensity. Apparent binding constants were determined and ranged between 1.22 and 23.96 mu M-1. The present data suggest that the novel fluorinated styryl benzazole derivatives may prove useful for the design of F-18-labeled amyloid radioprobes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.065

文献信息

• 一种吡啶类链状共轭体系分子衍生物及其制备方法和应用
  申请人：郑州大学

  公开号：CN109776583A

  公开（公告）日：2019-05-21

  本发明公开了一种吡啶类链状共轭体系分子衍生物及其制备方法和应用，涉及有机合成技术领域。本发明化合物具有通式1、通式2、通式3或通式4共四种结构；其中，R1为溴、甲基、叔丁基、甲氧基、酯基或酰胺基；m为2或3；通式2中的R2溴、酯基、酰胺基或羧基；R3为氢、氟、甲基、甲氧基、酯基或酰胺基；通式3或通式4中的X为碳原子或氮原子；R4为氢、甲基、氟、氯、溴或硝基；Y为碳原子或氮原子；Z为亚氨基或氧原子。本发明合成的化合物对鱼藤酮诱导的PC12细胞损伤有较明显保护作用，并对α‑Syn蛋白聚集和纤维化有明显抑制作用，具有统计学意义，可能进一步开发成为用于治疗帕金森的药物；通式1～通式4分别为：
• Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogs
  作者：Jacob M. Hoffman、Anthony M. Smith、Clarence S. Rooney、Thorsten E. Fisher、John S. Wai、Craig M. Thomas、Dona L. Bamberger、James L. Barnes、Theresa M. Williams

  DOI：10.1021/jm00060a002

  日期：1993.4

  A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalmido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB. One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229),

  基于初步开发的3-[（（邻苯二甲酰亚胺基）乙基] -5-乙基-6-甲基吡啶-2（1H）-一]（3）铅，开发了一系列新的有效的特定2-吡啶酮逆转录酶（RT）抑制剂，一种非核苷衍生物，在细胞培养中对HIV-1株IIIB表现出弱的抗病毒活性。一种化合物3-[（苯并恶唑-2-基）乙基] -5-乙基-6-甲基吡啶-2（1H）-一（9，L-696,229），是RT酶的高度选择性拮抗剂（IC50 （= 23 nM）且在MT4人T淋巴细胞培养物中（CIC95 = 50-100 nM）将HIV-1 IIIB感染的传播抑制> 95％（CIC95 = 50-100 nM），作为抗病毒药物进行临床评估。
• Hydroxylated inhibitors of HIV reverse transcriptase
  申请人：MERCK & CO. INC.

  公开号：EP0481802A1

  公开（公告）日：1992-04-22

  Novel biotransformed or synthetic hydroxy pyridinones inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts (where appropriate), pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  新型生物转化或合成的羟基吡啶酮抑制HIV逆转录酶，在预防或治疗HIV感染以及治疗艾滋病方面具有用途，可以作为化合物、药学上可接受的盐（如适用）、药用组合成分，无论是否与其他抗病毒药物、抗感染药物、免疫调节剂、抗生素或疫苗结合。还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。
• Microbial transformation of a substituted pyridinone using
  申请人：Merck & Co., Inc.

  公开号：US05185251A1

  公开（公告）日：1993-02-09

  Fermentation of the microorganism Actinoplanacete sp. (MA6559), ATTC No. 53771, in the presence of the HIV reverse transcriptase inhibitor ##STR1## yields 3-[2-(benzoxazol-2-yl)ethyl]-5-(1-hydroxyethyl)-6-methyl-2(1H)-pyridinone and 3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-hydroxymethyl-2(1H)-pyridinone, both of which are useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

  微生物Actinoplanacete sp. (MA6559)， ATTC No. 53771在存在HIV反转录酶抑制剂##STR1##的情况下发酵，产生3-[2-(苯并咪唑-2-基)乙基]-5-(1-羟乙基)-6-甲基-2(1H)-吡啶酮和3-[2-(苯并咪唑-2-基)乙基]-5-乙基-6-羟甲基-2(1H)-吡啶酮，两者均可用于预防或治疗HIV感染和治疗艾滋病。
• Inhibitors of HIV reverse transcriptase
  申请人：MERCK & CO. INC.

  公开号：EP0462800A2

  公开（公告）日：1991-12-27

  Novel pyridones inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by IV are also described.

  新型吡啶酮类药物可抑制艾滋病病毒逆转录酶，可用于预防或治疗艾滋病病毒感染和治疗艾滋病，可作为化合物、药学上可接受的盐、药物组合成分，无论是否与其他抗病毒药、抗感染药、免疫调节剂、抗生素或疫苗联合使用。还描述了治疗艾滋病的方法和预防或治疗 IV 感染的方法。