5-ethyl-2'-deoxy-carbocyclic uridine | 174172-97-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 5-ethyl-2'-deoxy-carbocyclic uridine
• 英文别名: 5-ethyl-1-[(1R,3S,4R)-3-hydroxy-4-(hydroxymethyl)cyclopentyl]pyrimidine-2,4-dione
• CAS: 174172-97-5
• 化学式: C₁₂H₁₈N₂O₄
• 分子量: 254.286
• InChiKey: YFOKWCDOVVYABO-BBBLOLIVSA-N

物化性质

• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-ethyl-2'-deoxy-carbocyclic uridine 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.67h， 生成 Acetic acid (1S,2R,4R)-2-acetoxymethyl-4-[5-((E)-2-bromo-vinyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-cyclopentyl ester
  参考文献：
  名称：

  A Short High Yielding Synthesis of the Potent Anti-VZV Carbocyclic Nucleoside Analogue Carba-BVDU

  摘要：

  A short high yielding synthesis of the potent anti-varicella-zoster virus (VZV) carbocyclic nucleoside analogue carba-BVDU 1 starting from aminodiol 2 is described. Reaction of 2 with acyl carbamate 3 and subsequent ring closure under acidic conditions afforded 5-ethyl-2'-deoxy-4'a-carbauridine 5. In situ acetylation of 5 afforded 3',5'-di-O-acetyl-5-ethyl-2'-deoxy-4'a-carbauridine 6 in 78% overall yield from 2. Radical bromination of 6 with either bromine or NBS and subsequent treatment with triethylamine gave an efficient conversion to 3',5'-di-O-acetyl-5-(E)-(2-bromovinyl)-2'-deoxy-4'a-carbauridine 7. Deacetylation of 7 afforded 1 in an overall 45-53% yield from 2.

  DOI：

  10.1080/15257779508010722
• 作为产物：
  描述：

  (3E)-1,1,1-trichloro-3-(ethoxymethylidene)pentan-2-one 在 盐酸 、 氢氧化钾 、 ammonium hydroxide 、 三乙胺 、 N,N'-羰基二咪唑 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 水 、 甲苯 为溶剂， 反应 21.5h， 生成 5-ethyl-2'-deoxy-carbocyclic uridine
  参考文献：
  名称：

  A Short High Yielding Synthesis of the Potent Anti-VZV Carbocyclic Nucleoside Analogue Carba-BVDU

  摘要：

  A short high yielding synthesis of the potent anti-varicella-zoster virus (VZV) carbocyclic nucleoside analogue carba-BVDU 1 starting from aminodiol 2 is described. Reaction of 2 with acyl carbamate 3 and subsequent ring closure under acidic conditions afforded 5-ethyl-2'-deoxy-4'a-carbauridine 5. In situ acetylation of 5 afforded 3',5'-di-O-acetyl-5-ethyl-2'-deoxy-4'a-carbauridine 6 in 78% overall yield from 2. Radical bromination of 6 with either bromine or NBS and subsequent treatment with triethylamine gave an efficient conversion to 3',5'-di-O-acetyl-5-(E)-(2-bromovinyl)-2'-deoxy-4'a-carbauridine 7. Deacetylation of 7 afforded 1 in an overall 45-53% yield from 2.

  DOI：

  10.1080/15257779508010722

文献信息

• [EN] PYRIMIDINE NUCLEOSIDES<br/>[FR] NUCLEOSIDES DE PYRIMIDINE
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：WO1997006178A1

  公开（公告）日：1997-02-20

  (EN) Pyrimidine nucleoside derivatives of formula (I), wherein R1 to R8 each individually represent hydrogen, halogen, cyano, lower alkyl, halo-lower alkyl, lower alkoxy, lower cycloalkyl or aryl; or R1 and R2 together or R2 and R3 together or R3 and R4 together represent a fused benzene ring; R9 represents hydrogen or lower alkyl; R10 represents hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl-lower alkyl, lower cycloalkyl-lower alkyl, acyl, 2-pyrrolidinylcarbonyl or a group of the formula -C(O)-CH(R12)-NH2; R11 represents halogen, lower alkyl, halo-lower alkyl or lower cycloalkyl; R12 represents hydrogen, lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, amino-lower alkyl or (4-imidazolyl)-lower alkyl; W represents CH2, C(O) or C(S); X represents CH2 or O; Y represents hydrogen, fluorine or hydroxy; Z represents C(R13)(R14), O, S, SO, SO2, Si(R15)(R16) or N(R17); R13 and R14 each represent hydrogen, lower alkyl, halo-lower alkyl, aryl or aryl-lower alkyl or R13 and R14 together represent lower alkylene; R15 and R16 each represent lower alkyl; and R17 represents lower alkyl, and pharmaceutically acceptable salts of those compounds of formula (I) which are basic inhibit viral thymidine kinase and are useful as antiviral agents.(FR) La présente invention se rapporte à des dérivés de nucléosides de pyrimidine de formule (I), dans laquelle R1 à R8 représentent chacun individuellement hydrogène, halogène, cyano, alkyle inférieur, halo-alkyle inférieur, alkoxy inférieur, cycloalkyle inférieur ou aryle; ou R1 et R2 ensemble ou R2 et R3 ensemble ou R3 et R4 ensemble représentent un cycle condensé de benzène; R9 représente hydrogène ou alkyle inférieur; R10 représente hydrogène, alkyle inférieur, alkényle inférieur, alkynyle inférieur, aryle-alkyle inférieur, cycloalkyle inférieur-alkyle inférieur, acyle, 2-pyrrolidinylcarbonyle ou un groupe ayant pour formule -C(O)-CH(R12)-NH2; R11 représente halogène, alkyle inférieur, halo-alkyle inférieur ou cycloalkyle inférieur; R12 représente hydrogène, alkyle inférieur, aryle-alkyle inférieur, alkylthio inférieur-alkyle inférieur, amino-alkyle inférieur ou (4-imidazolyl)-alkyle inférieur; W représente CH2, C(O) ou C(S); X représente CH2 ou O; Y représente hydrogène, fluor ou hydroxy; Z représente C(R13)(R14), O, S, SO, SO2, Si(R15)(R16) ou N(R17); R13 et R14 représentent chacun hydrogène, alkyle inférieur, halo-alkyle inférieur, aryle ou aryle-alkyle inférieur ou R13 et R14 représentent ensemble alkylène inférieur; R15 et R16 représentent chacun alkyle inférieur; et R17 représente alkyle inférieur. Ces composés de formule (I) ainsi que leurs sels pharmaceutiquement acceptables, qui sont basiques, inhibent la thymidine kinase virale et sont utiles en tant qu'agents antiviraux.