(Z,S)-(+)-2-amino-6-allyloxy-9-[(2-hydroxymethyl)cyclopropylidenemethyl]purine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (Z,S)-(+)-2-amino-6-allyloxy-9-[(2-hydroxymethyl)cyclopropylidenemethyl]purine
• 英文别名: [(1S,2Z)-2-[(6-allyloxy-2-amino-purin-9-yl)methylene]cyclopropyl]methanol；[(1S,2Z)-2-[(2-amino-6-prop-2-enoxypurin-9-yl)methylidene]cyclopropyl]methanol
• 化学式: C₁₃H₁₅N₅O₂
• 分子量: 273.294
• InChiKey: XJBDFVSCLCIEBM-BZJXQOFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  烯丙醇 、 (Z,S)-(+)-2-amino-6-chloro-9-[(2-hydroxymethyl)cyclopropylidene]methylpurine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (Z,S)-(+)-2-amino-6-allyloxy-9-[(2-hydroxymethyl)cyclopropylidenemethyl]purine
  参考文献：
  名称：

  具有 6-烷氧基和 6-烷硫基取代的亚甲基环丙烷类似物的合成和抗病毒活性，这些类似物对人类疱疹病毒具有广谱抗病毒活性。

  摘要：

  据报道，亚甲基环丙烷核苷对许多人类疱疹病毒具有活性。此类中最活跃的化合物是环丙病毒 (CPV)，它对人类巨细胞病毒 (HCMV)、爱泼斯坦-巴尔病毒、人类疱疹病毒 6 和人类疱疹病毒 8 的两种变体都表现出良好的抗病毒活性。 CPV 在亚甲基环丙烷上有两个羟甲基环，但具有单个羟甲基的类似物，例如原型 (S)-synguanol，也具有活性并表现出更广泛的抗病毒活性，其中还包括乙型肝炎病毒和人类免疫缺陷病毒。在这里，合成了大量在嘌呤的 6 位具有醚和硫醚取代基的单羟甲基化合物，并评估了对一系列人类疱疹病毒的抗病毒活性。其中一些类似物的抗病毒活性比 CPV 更广，因为它们还抑制了单纯疱疹病毒 1 和 2 以及水痘-带状疱疹病毒的复制。有趣的是，这些化合物的抗病毒活性似乎取决于 HCMV UL97 激酶的活性，但相对不受 HSV 中胸苷激酶活性缺失的影响。这些数据合在一起表明这些类似物的作用机制不同于

  DOI：

  10.1128/aac.00429-13

文献信息

• 2-amino-9-[(2-hydroxymethyl) cyclopropylidenemethyl] purines as antiviral agents
  申请人：Zemlicka Jiri

  公开号：US09174990B2

  公开（公告）日：2015-11-03

  Compounds which are active against viruses have the following Formulas: wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR1, OR2, or SR3; R1 is selected from the group consisting of alkyl, alkenyl, alkynyl, and C4-18 cycloalkyl, any of which may be optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl; R2 is selected from the group consisting of C2-18 alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl, and aryl; and R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl.

  对病毒活性的化合物具有以下公式：其中B为2-氨基嘌呤-9-基，可以是未取代或在6位取代为NHR1、OR2或SR3；R1选自由烷基、烯基、炔基和C4-18环烷基的群组，其中任何一个可以选择性地取代为羟基、卤素、氨基、酰基、环烷基、杂环烷基和芳基中的一个或多个成员；R2选自C2-18烷基、烯基、炔基和环烷基的群组，其中任何一个可以是支链或直链，并且可以选择性地取代为羟基、卤素、氨基、酰基、环烷基、杂环烷基和芳基中的一个或多个成员；R3选自自由烷基、烯基、炔基和环烷基的群组，其中任何一个可以是支链或直链，并且可以选择性地取代为羟基、卤素、氨基、酰基、环烷基、杂环烷基和芳基中的一个或多个成员。
• 2-amino-9-[(2-hydroxymethyl) cyclopropylidenemethyl] purine antiviral agents
  申请人：Zemlicka Jiri

  公开号：US20050124582A1

  公开（公告）日：2005-06-09

  Compounds which are active against viruses have the following Formulas: wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR 1 , OR 2 , or SR 3 ; R 1 is selected from the group consisting of alkyl, alkenyl, alkynyl, and C 4-18 cycloalkyl, any of which may be optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl; R 2 is selected from the group consisting of C 2-18 alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl, and aryl; and R 3 is selected from the group consisting of alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl.

  具有抗病毒活性的化合物有如下式子： 其中 B 是 2-氨基嘌呤-9-基，它可以未被取代或在 6 位被 NHR 取代 1 ，OR 2 或 SR 3 ; R 1 选自由烷基、烯基、炔基和 C 4-18 环烷基，其中任一环烷基可被羟基、卤代、氨基、酰基、环烷基、杂环烷基和芳基中的一个或多个成员任选取代； R 2 选自由 C 2-18 烷基、烯基、炔基和环烷基组成的组，其中任一环烷基可以是支链或非支链的，并可选地被羟基、卤代、氨基、酰基、环烷基、杂环烷基和芳基组成的组中的一个或多个成员取代；以及 R 3 选自由烷基、烯基、炔基和环烷基组成的组，其中任一环烷基可支化或不支化，并可选被羟基、卤代、氨基、酰基、环烷基、杂环烷基和芳基组成的组中的一个或多个成员取代。
• Structure−Activity Relationships of (<i>S,Z</i>)-2-Aminopurine Methylenecyclopropane Analogues of Nucleosides. Variation of Purine-6 Substituents and Activity against Herpesviruses and Hepatitis B Virus
  作者：Xinchao Chen、Earl R. Kern、John C. Drach、Elizabeth Gullen、Yung-Chi Cheng、Jiri Zemlicka

  DOI：10.1021/jm0205245

  日期：2003.4.1

  A series of 13 new (S,Z)-2-aminopurine methylenecyclopropane analogues was synthesized, and their antiviral activity was investigated. The nucleophilic displacement of chlorine of 2-amino-6-chloropurine derivative 5 with allyl-, propargyl-, cyclopropylmethyl-, isopropyl-, benzyl-, cyclohexyl-, and 2-hydroxyethylamine gave N-6-alkyl compounds 2a, 2b, 2c, 2d, 2e, 2f, and 2g. A similar reaction of 5 with allyl, cyclopropylmethyl, propyl, or pentyl alcohol catalyzed by K2CO3 afforded O-6-alkyl analogues 3a, 3c, 3h and 3i. Propane- and pentanethiol furnished S-6-alkyl compounds 4h and 4i. The N-6-alkyl derivatives 2a, 2b, O-6 analogues 3a, 3c, 3h, 3i, and S-6 compounds 4h, 4i which were highly effective in all CMV assays and exhibited the lowest cytotoxicity in proliferating HFF cells appear to be good candidates for in vivo assays. Activity of new analogues against HSV-1 or HSV-2 was restricted to BSC-1 and Vero cultures. Compounds 2c, 2b, 3a and 3h were effective against EBV in one of two assays (Daudi or H-1). Analogues 3a and 4i were the most active anti-VZV agents whereas compounds 3h, 3i, and 4h inhibited the replication of HBV in a micromolar concentration range.
• NOVEL 2-AMINO-9-((2-HYDROXYMETHYL) CYCLOPROPYLIDENEMETHYL) PURINES AS ANTIVIRAL AGENTS
  申请人：WAYNE STATE UNIVERSITY

  公开号：EP1490015B1

  公开（公告）日：2009-09-23
• 2-Amino-9-[(2-hydroxymethyl) cyclopropylidenemethyl] purines as antiviral agents
  申请人：Zemlicka Jiri

  公开号：US20070225302A1

  公开（公告）日：2007-09-27

  Compounds which are active against viruses have the following Formulas: wherein B is 2-aminopurine-9-yl, which may be unsubstituted or substituted in the 6 position with NHR 1 , OR 2 , or SR 3 ; R 1 is selected from the group consisting of alkyl, alkenyl, alkynyl, and C 4-18 cycloalkyl, any of which may be optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl; R 2 is selected from the group consisting of C 2-18 alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl, and aryl; and R 3 is selected from the group consisting of alkyl, alkenyl, alkynyl, and cycloalkyl, any of which may be branched or unbranched and optionally substituted with one or more members of the group consisting of hydroxy, halo, amino, acyl, cycloalkyl, heterocyclyl and aryl.