5-methyl-1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]pyrimidine-2,4-(1H,3H)-dione | 55360-18-4

• 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: 5-methyl-1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]pyrimidine-2,4-(1H,3H)-dione
• 英文别名: 1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-methylpyrimidine-2,4(1H,3H)-dione；1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-5-methyl-1H-pyrimidine-2,4-dione；1H-Pyrimidine-2,4-dione, 1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-5-methyl-；1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-5-methylpyrimidine-2,4-dione
• CAS: 55360-18-4
• 化学式: C₁₁H₁₆N₂O₄
• 分子量: 240.259
• InChiKey: HWIGLXQJOUDXCX-UHFFFAOYSA-N

物化性质

• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  胸腺嘧啶 、 2,2-二甲基-1,3-二氧环戊基-4-甲醇对甲基苯磺酸酯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 以39%的产率得到5-methyl-1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]pyrimidine-2,4-(1H,3H)-dione
  参考文献：
  名称：

  Bifunctional Acyclic Nucleoside Phosphonates. 1. Symmetrical 1,3-Bis[(phosphonomethoxy)propan-2-yl] Derivatives of Purines and Pyrimidines

  摘要：

  我们在这里报告了一种合成新的无环核苷酸对称双膦酸的一般方法。嘧啶和嘧啶碱的1,3-双[(二异丙氧磷酰基)甲氧基]衍生物通过它们与1,3-双[(二异丙氧磷酰基)甲氧基]丙烷-2-基对甲苯磺酸酯的反应制备。胞嘧啶、尿嘧啶和胸腺嘧啶提供了具有特定区域选择性的N1异构体。这种烷基化的区域选择性也适用于其他几种主要和次要醇的对甲苯磺酸酯。6-氯嘌呤和2-氨基-6-氯嘌呤在N9位烷基化。所得的双膦酸酯被转化为相应的自由膦酸，并进行了抗病毒和细胞毒活性测试。尽管目前尚未发现任何生物活性，但这项工作的结果可以作为合成新型无环核苷酸膦酸酯（ANP）的有用工具。

  DOI：

  10.1135/cccc20060543

文献信息

• [EN] PHOSPHONATE NUCLEOSIDES USEFUL IN THE TREATMENT OF VIRAL DISEASES<br/>[FR] NUCLÉOSIDES PHOSPHONATES UTILES DANS LE TRAITEMENT DE MALADIES VIRALES
  申请人：UNIV CORK

  公开号：WO2015177351A1

  公开（公告）日：2015-11-26

  The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or prodrug thereof, and their use in medicine particular as anti-viral agents; wherein: Base is a natural or non-natural nucleobase, and the other substituents are as defined in the claims.

  本发明涉及一种式(I)的化合物，或其在药学上可接受的盐或前药，以及它们在医学上特别作为抗病毒剂的用途；其中：基团是天然或非天然的核碱基，其他取代基如权利要求中所定义。
• Phosphonate nucleosides useful in the treatment of viral diseases
  申请人：University College Cork

  公开号：US10167302B2

  公开（公告）日：2019-01-01

  The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or prodrug thereof, and their use in medicine particular as anti-viral agents; wherein: X is selected from O and NR11; Y is selected from O, S and NR12; A is selected from —(CR1R2)n-, —(CR9R10)—, —(CR9R10)—(CR1R2)n-, —(CR1R3)—(CR2R4)—(CR1R2)n-, —CR3═CR4—(CR1R2)n- and —C≡C—(CR1R2)n-; R1 and R2 are independently selected from H, alkyl, hydroxyl, hydroxymethyl and halogen; R3 and R4 are independently selected from H and alkyl, or R3 and R4 together with the carbon atoms to which they are attached form a mono or bicyclic ring system selected from cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl; R5 is selected from H, P(═O)(OH)2 and P(═O)(OH)—O—P(═O)(OH)2; R6 is selected from H and alkyl; R7 and R8 are independently selected from H, alkyl, halogen and hydroxymethyl R9 and R19 together with the carbon atoms to which they are attached form a mono or bicyclic ring system selected from cycloalkyl, cycloalkenyl, heterocycloalkyl and heterocycloalkenyl; R11 is selected from H and alkyl; R12 is selected from H and alkyl; m is 0, 1, 2 or 3; n is 1, 2 or 3; p is 0 or 1; q is 0, 1, 2 or 3; r is 0, 1, 2, 3, 4 or 5; s is 0 or 1; Base is a natural or non-natural nucleobase, and wherein each alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl may be optionally substituted as described herein.

  本发明涉及式（I）化合物或其药学上可接受的盐或原药，以及它们在医药中的用途，特别是作为抗病毒剂； 其中 X 选自 O 和 NR11； Y 选自 O、S 和 NR12； A 选自-(CR1R2)n-、-(CR9R10)-、-(CR9R10)-(CR1R2)n-、-(CR1R3)-(CR2R4)-(CR1R2)n-、-CR3═CR4-(CR1R2)n-和-C≡C-(CR1R2)n-； R1 和 R2 独立选自 H、烷基、羟基、羟甲基和卤素； R3 和 R4 独立选自 H 和烷基，或 R3 和 R4 与它们所连接的碳原子一起形成选自环烷基、环烯基、杂环烷基、杂环烯基、芳基和杂芳基的单环或双环系统； R5 选自 H、P(═O)(OH)2 和 P(═O)(OH)-O-P(═O)(OH)2； R6 选自 H 和烷基； R7 和 R8 独立地选自 H、烷基、卤素和羟甲基 R9 和 R19 与它们所连接的碳原子一起形成一个单环或双环系统，该系统选自环烷基、环烯基、杂环烷基和杂环烯基； R11 选自 H 和烷基； R12 选自 H 和烷基； m 是 0、1、2 或 3； n是1、2或3 p 是 0 或 1 q 是 0、1、2 或 3； r 是 0、1、2、3、4 或 5； s 是 0 或 1； 碱基是天然或非天然核碱基，以及 其中每个烷基、环烷基、环烯基、杂环烷基、杂环烯基、芳基和杂芳基可以如本文所述被任选取代。
• PHOSPHONATE NUCLEOSIDES USEFUL IN THE TREATMENT OF VIRAL DISEASES
  申请人：University College Cork

  公开号：US20170218001A1

  公开（公告）日：2017-08-03

  The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or prodrug thereof, and their use in medicine particular as anti-viral agents; wherein: X is selected from O and NR 11 ; Y is selected from O, S and NR 12 ; A is selected from —(CR 1 R 2 )n-, —(CR 9 R 10 )—, —(CR 9 R 10 )—(CR 1 R 2 )n-, —(CR 1 R 3 )—(CR 2 R 4 )—(CR 1 R 2 )n-, —CR 3 ═CR 4 —(CR 1 R 2 )n- and —C≡C—(CR 1 R 2 )n-; R 1 and R 2 are independently selected from H, alkyl, hydroxyl, hydroxymethyl and halogen; R 3 and R 4 are independently selected from H and alkyl, or R 3 and R 4 together with the carbon atoms to which they are attached form a mono or bicyclic ring system selected from cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl; R 5 is selected from H, P(═O)(OH) 2 and P(═O)(OH)—O—P(═O)(OH) 2 ; R 6 is selected from H and alkyl; R 7 and R 8 are independently selected from H, alkyl, halogen and hydroxymethyl R 9 and R 19 together with the carbon atoms to which they are attached form a mono or bicyclic ring system selected from cycloalkyl, cycloalkenyl, heterocycloalkyl and heterocycloalkenyl; R 11 is selected from H and alkyl; R 12 is selected from H and alkyl; m is 0, 1, 2 or 3; n is 1, 2 or 3; p is 0 or 1; q is 0, 1, 2 or 3; r is 0, 1, 2, 3, 4 or 5; s is 0 or 1; Base is a natural or non-natural nucleobase, and wherein each alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl may be optionally substituted as described herein.
• Bifunctional Acyclic Nucleoside Phosphonates. 1. Symmetrical 1,3-Bis[(phosphonomethoxy)propan-2-yl] Derivatives of Purines and Pyrimidines
  作者：Silvie Vrbovská、Antonín Holý、Radek Pohl、Milena Masojídková

  DOI：10.1135/cccc20060543

  日期：——

  We report here a general method for the synthesis of new symmetrical bis-phosphonates of acyclic nucleosides. 1,3-Bis[(diisopropoxyphosphoryl)methoxy] derivatives of purine and pyrimidine bases were prepared by their reaction with 1,3-bis[(diisopropoxyphosphoryl)-methoxy]propan-2-yl tosylate. Cytosine, uracil and thymine provided regiospecificallyN¹-isomers. This alkylation regiospecificity applies to several other tosylates of primary and secondary alcohols as well. 6-Chloropurine and 2-amino-6-chloropurine were alkylated in N⁹position. Resulting bis-phosphonates were converted to the respective free phosphonic acids and tested for antiviral and cytostatic activity. Despite the fact that no biological activity was found so far, the outcome of this work can serve as a useful tool in synthesis of novel groups of acyclic nucleoside phosphonates (ANPs).

  我们在这里报告了一种合成新的无环核苷酸对称双膦酸的一般方法。嘧啶和嘧啶碱的1,3-双[(二异丙氧磷酰基)甲氧基]衍生物通过它们与1,3-双[(二异丙氧磷酰基)甲氧基]丙烷-2-基对甲苯磺酸酯的反应制备。胞嘧啶、尿嘧啶和胸腺嘧啶提供了具有特定区域选择性的N1异构体。这种烷基化的区域选择性也适用于其他几种主要和次要醇的对甲苯磺酸酯。6-氯嘌呤和2-氨基-6-氯嘌呤在N9位烷基化。所得的双膦酸酯被转化为相应的自由膦酸，并进行了抗病毒和细胞毒活性测试。尽管目前尚未发现任何生物活性，但这项工作的结果可以作为合成新型无环核苷酸膦酸酯（ANP）的有用工具。