1-[5-({[4-(Dichloromethyl)-2-oxido-4H-1,3,2-benzodioxaphosphinin-2-yl]oxy}methyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione | 676457-84-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 1-[5-({[4-(Dichloromethyl)-2-oxido-4H-1,3,2-benzodioxaphosphinin-2-yl]oxy}methyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-[(2R,5S)-5-[[4-(dichloromethyl)-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 676457-84-4
• 化学式: C₁₈H₁₇Cl₂N₂O₇P
• 分子量: 475.222
• InChiKey: ZCEIGMROYJJQEA-PUFDXKOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[5-({[4-(Dichloromethyl)-2-oxido-4H-1,3,2-benzodioxaphosphinin-2-yl]oxy}methyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione 在 phosphate buffer 作用下， 生成 Phosphoric acid 2,2-dichloro-1-(2-hydroxy-phenyl)-ethyl ester (2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,5-dihydro-furan-2-ylmethyl ester
  参考文献：
  名称：

  d4TMP Delivery from 7-SubstitutedcycloSal-d4TMPs

  摘要：

  Benzyl-substituted cycloSal-d4T monophosphates were prepared and evaluated for their ability to release d4TMP selectively. In contrast to previously reported derivatives, two of the new compounds release d4TMP as the sole product while two others gave the expected benzyl phosphate diesters. However, these diesters were surprisingly stable against degradation to release d4TMP.

  DOI：

  10.1081/ncn-120022663
• 作为产物：
  描述：

  司他夫定 在 叔丁基过氧化氢 、 N,N-二异丙基乙胺 作用下， 以 癸烷 、 乙腈 为溶剂， 生成 1-[5-({[4-(Dichloromethyl)-2-oxido-4H-1,3,2-benzodioxaphosphinin-2-yl]oxy}methyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Interaction of cycloSal-Pronucleotides with Cholinesterases from Different Origins. A Structure−Activity Relationship

  摘要：

  A large number of cycloSal-nucleotide triesters 1-49 have been studied concerning their ability to inhibit cholinesterases of different origins as well as to inhibit HIV replication in cell culture. It was shown that none of the triesters showed inhibitory effects against human acetylcholinesterase (AChE; isolated enzyme) as well as against AChE from beef erythrocytes and calf serum. In contrast, inhibition of butyrylcholinesterase (BChE) has been observed for some triesters in human and mouse serum. cycloSal pronucleotides showed strong competitive inhibition with respect to the substrate acetylcholine chloride (K-i/K-m: similar to2 x 10(-5)) and acted by time-dependent irreversible inhibition of the human serum BChE. Detailed studies demonstrated that the inhibitory effect against BChE is dependent on the nucleoside analogue, the substitution pattern of the cycloSal-moiety, and particularly on the stereochemistry at the phosphorus atom. Structural requirements to avoid the inhibition of BChE by cycloSal-nucleotide triesters have been elucidated in the reported study.

  DOI：

  10.1021/jm031032a