N²-(p-anisyldiphenylmethyl)-9-[(2-hydroxyethoxy)methyl]guanine | 103024-95-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N²-(p-anisyldiphenylmethyl)-9-[(2-hydroxyethoxy)methyl]guanine
• 英文别名: N²-(p-anisyldiphenylmethyl)-9-<(2-hydroxyethoxy)methyl>guanine；2N-(monomethoxytrityl)aciclovir；9-(2-hydroxyethoxymethyl)-2-[[(4-methoxyphenyl)-diphenylmethyl]amino]-1H-purin-6-one
• CAS: 103024-95-9
• 化学式: C₂₈H₂₇N₅O₄
• 分子量: 497.553
• InChiKey: HBVQBHCSLJNALL-UHFFFAOYSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N²-(p-anisyldiphenylmethyl)-9-[(2-hydroxyethoxy)methyl]guanine 在 1H-1,2,4-三唑 、 N-甲基咪唑 、 水 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 9-[(2-hydroxyethoxy)methyl]guanine 2-chlorophenyl (3-hexadecyloxypropyl) phosphate
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice

  摘要：

  We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-I infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase.

  DOI：

  10.1080/15257770008033022
• 作为产物：
  描述：

  阿昔洛韦 在 甲醇 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N²-(p-anisyldiphenylmethyl)-9-[(2-hydroxyethoxy)methyl]guanine
  参考文献：
  名称：

  New potential prodrugs of aciclovir using calix[4]arene as a lipophilic carrier: synthesis and drug-release studies at the air–water interface

  摘要：

  两种四对叔丁基杯[4]芳烃物种通过碳酯键在下缘连接着一个或两个抗HSV阿昔洛韦单元，被合成为可能的抗病毒前药。使用Langmuir平衡在空气-水和空气-碳酸盐缓冲界面研究了这些衍生物的两亲性；形成的单层在两个亚相上都是稳定的。然后在pH 10和37°C的碳酸盐缓冲亚相上用这些分子形成的单层来监测二酯键的水解。通过HPLC观察到两种衍生物在3天内释放出约30%的游离阿昔洛韦。

  DOI：

  10.1039/c2nj40338b

文献信息

• Synthesis and anti-herpes virus activity of acyclic 2'-deoxyguanosine analogs related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine
  作者：John C. Martin、Danny P. C. McGee、Gary A. Jeffrey、Doug W. Hobbs、Donald F. Smee、Thomas R. Matthews、Julian P. H. Verheyden

  DOI：10.1021/jm00158a011

  日期：1986.8

  Several "sugar" modified acyclic nucleoside analogues related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 2) were synthesized and evaluated for antiviral activity. The preparation generally involved the condensation of the acetoxymethyl ether of alcohols 6c-g and 10-12a with diacetylguanine to give adducts 7c-g and 14-16, which were then deprotected to afford analogues 9c-g and 17-19. Alternatively

  合成了几种与9-[（1,3-二羟基-2-丙氧基）甲基]鸟嘌呤（DHPG，2）有关的“糖”修饰的无环核苷类似物，并评估了其抗病毒活性。制备通常涉及将醇6c-g和10-12a的乙酰氧基甲基醚与二乙酰鸟嘌呤缩合，得到加合物7c-g和14-16，然后将其脱保护得到类似物9c-g和17-19。或者，将醇12a和13a通过它们的甲苯磺酸酯12b和13b转化为碘化物，然后与鸟嘌呤的钠盐反应，得到脱保护后的类似物22和23。醛27上的醛醇-Cannizzaro交叉反应容易得到28，其脱保护得到类似物29。针对HSV-1的体外分析表明，所测试的所有化合物的活性均低于DHPG，尽管有几种是病毒胸苷激酶的良好底物。在小鼠脑炎模型中评估了更有前途的无环核苷9c，19和29，并证明在20 mg / kg的剂量下无法有效预防死亡。
• Non-covalent hitchhiking on endogenous carriers as a protraction mechanism for antiviral macromolecular prodrugs
  作者：Camilla Kaas Frich、Franziska Krüger、Raoul Walther、Cecilie Domar、Anna H.F. Andersen、Anne Tvilum、Frederik Dagnæs-Hansen、Paul W. Denton、Martin Tolstrup、Søren R. Paludan、Jan Münch、Alexander N. Zelikin

  DOI：10.1016/j.jconrel.2018.12.016

  日期：2019.1

  at a time. In turn, macromolecular prodrugs (MP) are advantaged in carrying a high drug payload but offering only a modest extension of residence time to the conjugated drugs. In this work, we engineer MP to contain terminal groups that bind to albumin via non-covalent association and reveal that this facile measure affords a significant protraction for the associated polymers. This methodology is

  白蛋白是一种非常成功的药物输送工具，为相关货物提供了显着延长的身体和血液停留时间，但一次只能贩运单份药物。反过来，大分子前药（MP）在携带高药物有效载荷方面具有优势，但对缀合药物的滞留时间仅适度延长。在这项工作中，我们对MP进行了工程改造，使其包含通过非共价结合与白蛋白结合的末端基团，并揭示了这种简便的方法为相关的聚合物提供了显着的优势。该方法适用于阿昔洛韦的MP，阿昔洛韦是一种成功的抗单纯疱疹病毒感染药物，但药代动力学较差。所得的白蛋白仿射MP在体外和体内都是有效的抗2型单纯疱疹病毒（HSV-2）的药物。在后一种情况下，皮下注射MP会产生局部（阴道）抗病毒作用和全身保护作用。与白蛋白的非共价结合所带来的好处可以很容易地转移到正在开发的多种MP中，作为抗癌，抗炎和抗病毒的手段来进行药物递送。
• Synthesis and Antiviral Evaluation of 1-O-Hexadecylpropanediol-3-P-acyclovir: Efficacy Against HSV-1 Infection in Mice
  作者：James R. Beadle、Ganesh D. Kini、Kathy A. Aldern、Michael F. Gardner、Kristine N. Wright、Rachel J. Rybak、Earl R. Kern、Karl Y. Hostetler

  DOI：10.1080/15257770008033022

  日期：2000.1

  We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-I infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase.
• New potential prodrugs of aciclovir using calix[4]arene as a lipophilic carrier: synthesis and drug-release studies at the air–water interface
  作者：Guillaume Sautrey、Igor Clarot、Ewa Rogalska、Jean-Bernard Regnouf-de-Vains

  DOI：10.1039/c2nj40338b

  日期：——

  Two tetra-p-tert-butyl-calix[4]arene species bearing one or two anti-HSV aciclovir units tethered via carbodiester linkages at the lower rim were synthesized as possible antiviral prodrugs. The amphiphilic properties of these derivatives were studied using Langmuir balance at the air–water and air–carbonate buffer interfaces; the monolayers formed were stable on both subphases. Monolayers formed with these molecules on a carbonate buffer subphase at pH 10 and 37 °C were then used for monitoring hydrolysis of the diester linkage. The release of free aciclovir of around 30% in 3 days was observed with both derivatives, as shown with HPLC.

  两种四对叔丁基杯[4]芳烃物种通过碳酯键在下缘连接着一个或两个抗HSV阿昔洛韦单元，被合成为可能的抗病毒前药。使用Langmuir平衡在空气-水和空气-碳酸盐缓冲界面研究了这些衍生物的两亲性；形成的单层在两个亚相上都是稳定的。然后在pH 10和37°C的碳酸盐缓冲亚相上用这些分子形成的单层来监测二酯键的水解。通过HPLC观察到两种衍生物在3天内释放出约30%的游离阿昔洛韦。