1-[(1'S,2'R)-1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl-5-ethynyl-2,4(1H,3H)-pyrimidinedione

• 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-[(1'S,2'R)-1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl-5-ethynyl-2,4(1H,3H)-pyrimidinedione
• 英文别名: 1-[1'S,2'R-bis(hydroxymethyl)-cyclopropan-1'-yl]methyl-5-ethynyl-2,4(1H,3H)-pyrimidinedione；1-[[(1S,2R)-1,2-bis(hydroxymethyl)cyclopropyl]methyl]-5-ethynyl-pyrimidine-2,4-dione；1-[[(1S,2R)-1,2-bis(hydroxymethyl)cyclopropyl]methyl]-5-ethynylpyrimidine-2,4-dione
• 化学式: C₁₂H₁₄N₂O₄
• 分子量: 250.254
• InChiKey: DTSHCWVQXCXVIX-CABZTGNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-乙炔-2,4(1h,3H-)-嘧啶二酮(9ci) 在 盐酸 、 18-冠醚-6 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 1-[(1'S,2'R)-1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl-5-ethynyl-2,4(1H,3H)-pyrimidinedione
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Novel Anti-VZV 5-Substituted Uracil Nucleosides with a Cyclopropane Sugar Moiety

  摘要：

  A series of 5-substituted uracil nucleoside derivatives with a 1(1'S,2'R)-[1',2'-bis(hydroxymethyl)-cycloproplyl]methyl group as an acyclosugar moiety were synthesized and evaluated for their anti-herpetic activities. Among the compounds synthesized, (E)-5-halovinyluracil derivatives showed superior anti-varicella tester virus (VZV) activity over acyclovir (ACV) but were less potent than ACV against herpes symplex virus type-1 (HSV-1). IC50 values for the VZV Kawaguchi strain were 0.027 for Br, 0.070 for Cl, and 0.054 mu g/mL for I derivatives and 3.4 mu g/mL for ACV. The most potent compound, (1'S,2'R)-5-[(E)-2-bromoethenyl]-1-[[1', (hydroxymethyl)cycloprop-1'-yl]methyl]-2,4-(1H,3H)-pyrimidinedione (3a), was 40-60-fold more potent than ACV against clinical isolates of VZV. It showed good oral bioavailability in rats (68.5%) and, unlike (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), did not result in the release of (E)-5-(2-bromovinyl)uracil (BVU), a potent dihydropyrimidine dehydrogenase inhibitor, in plasma after oral administration.

  DOI：

  10.1021/jm9904194

文献信息

• Cyclopropane derivatives and anti-viral agent containing the same
  申请人：Ajinomoto Co., Inc.

  公开号：US05496824A1

  公开（公告）日：1996-03-05

  The present invention provides a pharmaceutical agent having a high pharmaceutical potency against varicella-zoster viruses and herpes simplex viruses, compositions containing the same, and methods for treating varicella-zoster viruses using the same.

  本发明提供了一种具有高抗水痘-带状疱疹病毒和单纯疱疹病毒药效的药物制剂，含有该药物制剂的组合物，以及使用该药物制剂治疗水痘-带状疱疹病毒的方法。
• Bis(hydroxymethyl)cyclopropylmethyl pyrimidine derivatives, their preparation and their use as anti-viral agents
  申请人：Ajinomoto Co., Inc.

  公开号：EP0649840A1

  公开（公告）日：1995-04-26

  Cyclopropane derivatives of the following general formula (I) or their pharmaceutically acceptable salts, are provided, as well as anti-viral agents containing the same as the active ingredient: wherein R¹ and R², which may be the same or different, each represents a hydrogen atom or an acyl group; R³ represents a halogen atom, a 2-haloalkyl group, a 2-halo-1-alkenyl group, or a 1-alkynyl group. The derivatives and their salts have anti-viral activity, for example against varicella zoster and herpes simplex, and may be used as alternatives to acyclovir. And intermediates of formulae (3) and (9) wherein R₄ is a protective group for a hydroxyl group and R₃ is defined as above.

  提供了以下通式（I）的环丙烷衍生物或其药学上可接受的盐类，以及含有相同活性成分的抗病毒制剂： 其中R¹和R²可以相同或不同，各自代表氢原子或酰基；R³代表卤素原子、2-卤代烷基、2-卤代-1-烯基或1-炔基。这些衍生物及其盐类具有抗病毒活性，例如抗水痘带状疱疹和单纯疱疹，可用作阿昔洛韦的替代品。以及式 (3) 和 (9) 的中间体 其中 R₄ 是羟基的保护基团，R₃ 的定义同上。
• US5496824A
  申请人：——

  公开号：US5496824A

  公开（公告）日：1996-03-05
• Synthesis and Antiviral Activity of Novel Anti-VZV 5-Substituted Uracil Nucleosides with a Cyclopropane Sugar Moiety
  作者：Tomoyuki Onishi、Chika Mukai、Ryusuke Nakagawa、Takaaki Sekiyama、Miho Aoki、Katsuya Suzuki、Harumi Nakazawa、Nobukazu Ono、Yuko Ohmura、Satoshi Iwayama、Masahiko Okunishi、Takashi Tsuji

  DOI：10.1021/jm9904194

  日期：2000.1.1

  A series of 5-substituted uracil nucleoside derivatives with a 1(1'S,2'R)-[1',2'-bis(hydroxymethyl)-cycloproplyl]methyl group as an acyclosugar moiety were synthesized and evaluated for their anti-herpetic activities. Among the compounds synthesized, (E)-5-halovinyluracil derivatives showed superior anti-varicella tester virus (VZV) activity over acyclovir (ACV) but were less potent than ACV against herpes symplex virus type-1 (HSV-1). IC50 values for the VZV Kawaguchi strain were 0.027 for Br, 0.070 for Cl, and 0.054 mu g/mL for I derivatives and 3.4 mu g/mL for ACV. The most potent compound, (1'S,2'R)-5-[(E)-2-bromoethenyl]-1-[[1', (hydroxymethyl)cycloprop-1'-yl]methyl]-2,4-(1H,3H)-pyrimidinedione (3a), was 40-60-fold more potent than ACV against clinical isolates of VZV. It showed good oral bioavailability in rats (68.5%) and, unlike (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), did not result in the release of (E)-5-(2-bromovinyl)uracil (BVU), a potent dihydropyrimidine dehydrogenase inhibitor, in plasma after oral administration.