(2RS,3SR)-4-[({4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-[(methylsulfanyl)methyl]butane-1,2-diol trifluoroacetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: (2RS,3SR)-4-[({4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-[(methylsulfanyl)methyl]butane-1,2-diol trifluoroacetate
• 英文别名: (4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl-[(2S,3R)-3,4-dihydroxy-2-(methylsulfanylmethyl)butyl]azanium;2,2,2-trifluoroacetate
• 化学式: C₂HF₃O₂*C₁₃H₂₁N₅O₂S
• 分子量: 425.432
• InChiKey: ZWCNRCGJCKEIQJ-UXQCFNEQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  183
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  5-[(benzyloxy)methyl]-4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde 在 sodium azide 、 sodium cyanoborohydride 、 三甲基膦 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.09h， 生成 (2RS,3SR)-4-[({4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-[(methylsulfanyl)methyl]butane-1,2-diol trifluoroacetate
  参考文献：
  名称：

  Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics

  摘要：

  Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and coupled via a methylene link to 9-deazaadenine. The products were tested for inhibition against human MTAP and Escherichia coli and Neisseria meningitidis MTANs and gave K-i values as low as 0.23 nM. These results were compared to those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-D-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1-[9-deazaadenin-9-yl)methyl]3-hydroxy-4-methylthiomethylpyrrolidine (MT-DADMe-Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of approximately 2- to 4-fold those of 3 but were significantly weaker than 4. Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another case, N-methylation of a side chain secondary amine resulted in a 250-fold loss of activity against the same enzyme [(+/-)-65 vs (+/-)-68]. The inhibition results were also contrasted with those acyclic derivatives previously prepared as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where some inhibitors in the latter case were found to be more potent than their cyclic counterparts. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.006