5-[(E)-2-bromoethenyl]-1-[[(1S,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octan-1-yl]methyl]pyrimidine-2,4-dione | 258334-04-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-[(E)-2-bromoethenyl]-1-[[(1S,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octan-1-yl]methyl]pyrimidine-2,4-dione
• CAS: 258334-04-2
• 化学式: C₂₅H₂₃BrN₂O₄
• 分子量: 495.373
• InChiKey: MTZZCAFBROMWQC-AOERKCTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[(E)-2-bromoethenyl]-1-[[(1S,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octan-1-yl]methyl]pyrimidine-2,4-dione 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 1-[1(S),2(R)-二(羟甲基)环丙基甲基]-5-[2(E)-溴乙烯基]尿苷
  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
• 作为产物：
  描述：

  二苯基重氮甲烷 在 锂硼氢 、 18-冠醚-6 、 四溴化碳 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.33h， 生成 5-[(E)-2-bromoethenyl]-1-[[(1S,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octan-1-yl]methyl]pyrimidine-2,4-dione
  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

• 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.