1-[2-(Phosphonomethoxy)ethyl]cytosine | 117087-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-[2-(Phosphonomethoxy)ethyl]cytosine
• 英文别名: PMEC；2-Phosphonylmethoxyethylcytosine；2-(4-amino-2-oxopyrimidin-1-yl)ethoxymethylphosphonic acid
• CAS: 117087-39-5
• 化学式: C₇H₁₂N₃O₅P
• 分子量: 249.163
• InChiKey: XXUKNWCJFNYLDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-(Phosphonomethoxy)ethyl]cytosine 在 triethylammonium hydrogensulfite 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 1-[2-(phosphonomethoxy)ethyl]-N⁴-allylcytosine
  参考文献：
  名称：

  Synthesis of N4-Substituted Derivatives of 1-[2-(Phosphonomethoxy)ethyl]cytosine and Its Diisopropyl Ester as a Model Reaction for the Synthesis of N4-Substituted Derivatives of Cidofovir

  摘要：

  我们研究了1-[2-(磷酸甲氧基)乙基]胞嘧啶（1）及其二异丙酯（2）与三乙胺硫酸氢盐在60%水甲醇中的反应。在一些一级或二级胺盐的存在下，反应在25-70℃下产生了转氨化衍生物4a-4e和5a，5b作为主要产物，伴随尿嘧啶化合物。然而，对于某些胺而言，反应失败了。

  DOI：

  10.1135/cccc20052066
• 作为产物：
  描述：

  1-<2-<(Diethylphosphonyl)methoxy>ethyl>cytosine 在 三甲基氯硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以81%的产率得到1-[2-(Phosphonomethoxy)ethyl]cytosine
  参考文献：
  名称：

  Synthesis and antiviral activity of the nucleotide analog (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cystosine

  摘要：

  The acyclic nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl] cytosine (2, HPMPC) was prepared on a multigram scale in 18% overall yield starting from (R)-2,3-O-isopropylideneglycerol. The key step in the nine-step synthetic route is coupling of cytosine with the side-chain derivative 8 which bears a protected phosphonylmethyl ether group. In vitro data showed that HPMPC has good activity against herpes simplex virus types 1 and 2, although it was 10-fold less potent than acyclovir [AVC, 9-[(2-hydroxyethoxy)methyl]guanine]. By comparison, HPMPC exhibited greater activity than ACV against a thymidine kinase deficient strain of HSV 1 and was more potent than ganciclovir [DHPG, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine] against human cytomegalovirus. In vivo, HPMPC showed exceptional potency against HSV 1 systemic infection in mice, having an ED50 of 0.1 mg/kg per day (ip) compared with 50 mg/kg per day for ACV. HPMPC was also more efficacious than ACV in the topical treatment of HSV 1 induced cutaneous lesions in guinea pigs.

  DOI：

  10.1021/jm00127a010

文献信息

• Structure−Antiviral Activity Relationship in the Series of Pyrimidine and Purine <i>N</i>-[2-(2-Phosphonomethoxy)ethyl] Nucleotide Analogues. 1. Derivatives Substituted at the Carbon Atoms of the Base
  作者：Antonín Holý、Jaroslav Günter、Hana Dvořáková、Milena Masojídková、Graciela Andrei、Robert Snoeck、Jan Balzarini、Erik De Clercq

  DOI：10.1021/jm9811256

  日期：1999.6.1

  the bases in the suitably modified intermediates bearing reactive functions at the base moiety. The diesters were converted to the corresponding monoesters by sodium azide treatment, while the free acids were obtained from the diester by successive treatment with bromotrimethylsilane and hydrolysis. None of the PME derivatives in the pyrimidine series, their 6-aza or 3-deaza analogues, exhibited any

  通过对烷基进行烷基化制备一系列嘌呤和嘧啶N- [2-（膦甲氧基）乙基]衍生物的二烷基酯，其在嘌呤碱的位置2、6或8或在嘧啶碱的位置2、4或5。在氢化钠，碳酸铯或1,8-二氮杂双环[5,4,0]十一碳-7-烯（DBU）存在下的二甲基甲酰胺中，与2-氯乙氧基甲基膦酸酯二酯形成合适的杂环碱。通过在适当修饰的中间体上对碱基进行转化，获得额外的衍生物，该中间体在碱基部分具有反应性功能。通过叠氮化钠处理将二酯转化为相应的单酯，同时通过依次用溴代三甲基硅烷处理和水解从二酯中获得游离酸。嘧啶系列中没有PME衍生物，它们的6-氮杂或3-氮杂类似物，除5-溴胞嘧啶衍生物外，对测试的DNA病毒或逆转录病毒均表现出任何活性。Cl，F或OH基团取代了PMEA中2位的腺嘌呤环，从而降低了其对所有测试的DNA病毒的活性。在0.07-2 microg / mL的浓度范围（EC50）中，PMEDAP对HSV-1，HSV-2
• ACYCLIC NUCLEOSIDE PHOSPHONATE DIESTERS
  申请人：The Regents of the University of California

  公开号：US20170002033A1

  公开（公告）日：2017-01-05

  The present disclosure relates, inter alia, to compositions and methods for treating viral diseases and cancer. There are disclosed lipophilic antiviral and anticancer acyclic nucleoside phosphonate diesters, preparation thereof, and methods of using the compounds to treat viral diseases and cancer.

  本公开涉及用于治疗病毒性疾病和癌症的组合物和方法，其中包括脂溶性抗病毒和抗癌无环核苷酸膦酸二酯，其制备方法以及使用这些化合物治疗病毒性疾病和癌症的方法。
• Method for polymerising vinyl monomers and/or oligomers comprising at least one vinyl radical
  申请人：——

  公开号：US20040225086A1

  公开（公告）日：2004-11-11

  The invention concerns a method for polymerising vinyl monomers and/or oligomers comprising at least a vinyl radical, which consists in mixing the vinyl monomer or the oligomer comprising at least a vinyl radical with: at least dioxygen supplying agent, at least a aldehyde representing for example between 1% and 15% of the weight of the mixture, at least an accelerator which may for example of consist in a metallic salt.

  本发明涉及一种聚合乙烯单体和/或寡聚物的方法，该乙烯单体和/或寡聚物至少包含一个乙烯基团，其方法包括将乙烯单体或至少包含一个乙烯基团的寡聚物与至少一个提供二氧化碳的剂，至少一个醛，例如占混合物重量的1％至15％，至少一种促进剂，例如可以是金属盐的混合。
• Acyclic nucleoside phosphonate diesters
  申请人：The Regents of the University of California

  公开号：US10076533B2

  公开（公告）日：2018-09-18

  The present disclosure relates, inter alia, to compositions and methods for treating viral diseases and cancer. There are disclosed lipophilic antiviral and anticancer acyclic nucleoside phosphonate diesters, preparation thereof, and methods of using the compounds to treat viral diseases and cancer.

  本公开主要涉及治疗病毒性疾病和癌症的组合物和方法。本发明公开了亲脂性抗病毒和抗癌无环核苷膦酸二酯、其制备方法以及使用该化合物治疗病毒性疾病和癌症的方法。
• Holy, Antonin; Rosenberg, Ivan; Dvorakova, Hana, Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 8, p. 2190 - 2210
  作者：Holy, Antonin、Rosenberg, Ivan、Dvorakova, Hana

  DOI：——

  日期：——