(Triphenyl-λ⁵-phosphanylidene)-acetic acid cyclopentyl ester | 1040888-43-4

• 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: (Triphenyl-λ⁵-phosphanylidene)-acetic acid cyclopentyl ester
• 英文别名: Cyclopentyl 2-(triphenyl-lambda5-phosphanylidene)acetate；cyclopentyl 2-(triphenyl-λ5-phosphanylidene)acetate
• CAS: 1040888-43-4
• 化学式: C₂₅H₂₅O₂P
• 分子量: 388.446
• InChiKey: OAVSJKHTTXZCMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (Triphenyl-λ⁵-phosphanylidene)-acetic acid cyclopentyl ester 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 生成 trans-(3'S,4S)-4-tert-Butoxycarbonylamino-5-(2'-oxopyrrolidin-3'-yl)pent-2-enoic Acid Cyclopentyl Ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 8. Pharmacological Optimization of Orally Bioavailable 2-Pyridone-Containing Peptidomimetics

  摘要：

  The optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors following oral administration to either beagle dogs or CM-monkeys is described. The molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an alpha,beta-unsaturated ester Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. Modification of the ester contained within these compounds is detailed along with alteration of the P-2 substituent present in the peptidomimetic portion of the inhibitors. The pharmacokinetics of several inhibitors in both dogs and monkeys are described (7 h plasma concentrations after oral administration) along with their human plasma stabilities, stabilities in incubations with human, dog, and monkey microsomes and hepatocytes, Caco-2 permeabilities, and aqueous solubilities. Compounds containing an alpha,beta-unsaturated ethyl ester fragment and either an ethyl or propargyl. P-2 moiety displayed the most promising combination of 3C enzyme inhibition (k(obs)/[1] 170 000-223 000 M-1 s(-1)), antiviral activity (EC50 = 0.047-0.058 muM, mean vs seven HRV serotypes), and pharmacokinetics following oral administration (7 h dog plasma levels = 0.248-0.682 muM; 7 h CM-monkey plasma levels = 0.057-0.896 muM).

  DOI：

  10.1021/jm030166l
• 作为产物：
  描述：

  2-溴乙酸环戊酯 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 19.17h， 生成 (Triphenyl-λ⁵-phosphanylidene)-acetic acid cyclopentyl ester
  参考文献：
  名称：

  光诱导分子间[4 + 2]环加成反应构建苯并双环[2.2.2]辛烷骨架

  摘要：

  探索了一种新型的高效合成高度取代的苯并双环[2.2.2]辛烷骨架的方法。在紫外光照射下，邻-二乙烯基苯经历周环反应以形成环状邻-喹二甲烷中间体，随后通过[4 + 2]加成使其与烯烃反应，从而在温和条件下构建苯并双环[2.2.2]辛烷骨架。革兰氏反应证明了该方案的合成潜力。

  DOI：

  10.1021/acs.joc.6b02547

文献信息

• Synthesis of Oxatricyclooctanes via Photoinduced Intramolecular Oxa-[4+2] Cycloaddition of Substituted <i>o</i>-Divinylbenzenes
  作者：Qiang Liu、Junlei Wang、Dazhi Li、Guo-Lin Gao、Chao Yang、Yuan Gao、Wujiong Xia

  DOI：10.1021/acs.joc.7b01055

  日期：2017.8.4

  The photolysis of substituted o-divinylbenzenes promotes a one-step and metal-free conversion to oxatricycles at room temperature. Irradiation o-divinylbenzenes results in an pericyclic reaction to form cyclic o-quinodiemthane intermediates, which subsequently undergo intramolecular oxa-[4+2] cycloaddition to form oxacyclic derivatives.

  在室温下，取代的邻二乙烯基苯的光解促进了一步和无金属的转化为氧三环。辐照邻二乙烯基苯导致周环反应，形成环状邻喹二乙烷中间体，随后中间体进行分子内的oxa- [4 + 2]环加成反应形成oxacyclic衍生物。
• [EN] ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS<br/>[FR] COMPOSES ET COMPOSITIONS ANTI-PICORNAVIRUS; UTILISATIONS PHARMACEUTIQUES ET MATERIAUX EMPLOYES POUR LEUR SYNTHESE
  申请人：AGOURON PHARMA

  公开号：WO2001040189A1

  公开（公告）日：2001-06-07

  Compounds of formula (I), where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of formula (II) where the formula variables are as defined herein that advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.

  本发明披露了式(I)的化合物，其中式变量如本文所定义，这些化合物有利地抑制或阻断了小肠病毒3C蛋白酶的生物活性。本发明还披露了式(II)的化合物，其中式变量如本文所定义，这些化合物有利地抑制或阻断了小肠病毒3C蛋白酶的生物活性。这些化合物以及含有这些化合物的药物组合物，对于治疗感染一种或多种小肠病毒（如鼻病毒3C蛋白酶）的患者或宿主非常有用。还描述了制备这些化合物的中间体和合成方法。
• ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1252145A1

  公开（公告）日：2002-10-30
• Photoinduced Intermolecular [4+2] Cycloaddition Reaction for Construction of Benzobicyclo[2.2.2]octane Skeletons
  作者：Qiang Liu、Junlei Wang、Dazhi Li、Chao Yang、Wujiong Xia

  DOI：10.1021/acs.joc.6b02547

  日期：2017.2.3

  skeletons has been explored. Under UV-light irradiation, o-divinylbenzenes underwent a pericyclic reaction to form the cyclic o-quinodimethane intermediates which were subsequently reacted with olefins through [4+2] addition to construct the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated the synthetic potential application of this protocol.

  探索了一种新型的高效合成高度取代的苯并双环[2.2.2]辛烷骨架的方法。在紫外光照射下，邻-二乙烯基苯经历周环反应以形成环状邻-喹二甲烷中间体，随后通过[4 + 2]加成使其与烯烃反应，从而在温和条件下构建苯并双环[2.2.2]辛烷骨架。革兰氏反应证明了该方案的合成潜力。
• Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 8. Pharmacological Optimization of Orally Bioavailable 2-Pyridone-Containing Peptidomimetics
  作者：Peter S. Dragovich、Thomas J. Prins、Ru Zhou、Theodore O. Johnson、Ye Hua、Hiep T. Luu、Sylvie K. Sakata、Edward L. Brown、Fausto C. Maldonado、Tove Tuntland、Caroline A. Lee、Shella A. Fuhrman、Leora S. Zalman、Amy K. Patick、David A. Matthews、Ellen Y. Wu、Ming Guo、Bennett C. Borer、Naresh K. Nayyar、Terence Moran、Lijian Chen、Paul A. Rejto、Peter W. Rose、Mark C. Guzman、Elena Z. Dovalsantos、Steven Lee、Kevin McGee、Michael Mohajeri、Andreas Liese、Junhua Tao、Maha B. Kosa、Bo Liu、Minerva R. Batugo、Jean-Paul R. Gleeson、Zhen Ping Wu、Jia Liu、James W. Meador、Rose Ann Ferre

  DOI：10.1021/jm030166l

  日期：2003.10.1

  The optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors following oral administration to either beagle dogs or CM-monkeys is described. The molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an alpha,beta-unsaturated ester Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. Modification of the ester contained within these compounds is detailed along with alteration of the P-2 substituent present in the peptidomimetic portion of the inhibitors. The pharmacokinetics of several inhibitors in both dogs and monkeys are described (7 h plasma concentrations after oral administration) along with their human plasma stabilities, stabilities in incubations with human, dog, and monkey microsomes and hepatocytes, Caco-2 permeabilities, and aqueous solubilities. Compounds containing an alpha,beta-unsaturated ethyl ester fragment and either an ethyl or propargyl. P-2 moiety displayed the most promising combination of 3C enzyme inhibition (k(obs)/[1] 170 000-223 000 M-1 s(-1)), antiviral activity (EC50 = 0.047-0.058 muM, mean vs seven HRV serotypes), and pharmacokinetics following oral administration (7 h dog plasma levels = 0.248-0.682 muM; 7 h CM-monkey plasma levels = 0.057-0.896 muM).