<3S-(3α,4β,5α)>-1--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: <3S-(3α,4β,5α)>-1--2,4(1H,3H)-pyrimidinedione
• 英文别名: 1-[(3S,4R,5S)-4,5-bis(hydroxymethyl)tetrahydrofuran-3-yl]pyrimidine-2,4-dione；1-[(3S,4R,5S)-4,5-bis(hydroxymethyl)oxolan-3-yl]pyrimidine-2,4-dione
• 化学式: C₁₀H₁₄N₂O₅
• 分子量: 242.232
• InChiKey: ASUZYLVDZUYEPF-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <3S-(3α,4β,5α)>-1--2,4(1H,3H)-pyrimidinedione 在 palladium diacetate 、 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 碘 、 硝酸 、 potassium hydrogencarbonate 、 三乙胺 、 三苯基膦 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 <3S-(3α(E),4β,5α)>-5-(2-bromoethenyl)-1--2,4(1H,3H)-pyrimidinedione
  参考文献：
  名称：

  Synthesis and antiviral activity of novel isonucleoside analogs

  摘要：

  A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3alpha,4beta,5alpha)]-2-amino-1,9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 muM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 muM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.

  DOI：

  10.1021/jm00061a013
• 作为产物：
  描述：

  <3S-(3α,4β,5α)>-1--3-furanyl>-2,4(1H,3H)-pyrimidinedione 在 palladium on activated charcoal 环己烯 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以60%的产率得到<3S-(3α,4β,5α)>-1--2,4(1H,3H)-pyrimidinedione
  参考文献：
  名称：

  Synthesis and antiviral activity of novel isonucleoside analogs

  摘要：

  A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3alpha,4beta,5alpha)]-2-amino-1,9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 muM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 muM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.

  DOI：

  10.1021/jm00061a013

文献信息

• Synthesis and antiviral activity of novel isonucleoside analogs
  作者：Joseph A. Tino、Junius M. Clark、A. Kirk Field、Glenn A. Jacobs、Karen A. Lis、Teresa L. Michalik、Bridgette McGeever-Rubin、William A. Slusarchyk、Steven H. Spergel

  DOI：10.1021/jm00061a013

  日期：1993.4

  A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3alpha,4beta,5alpha)]-2-amino-1,9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 muM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 muM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.