N-{9-[(3aR,4R,6R,6aR)-6-(3-Hydroxy-1-hydroxymethyl-2-nitro-propyl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-yl}-benzamide | 111269-00-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N-{9-[(3aR,4R,6R,6aR)-6-(3-Hydroxy-1-hydroxymethyl-2-nitro-propyl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-yl}-benzamide
• CAS: 111269-00-2
• 化学式: C₂₃H₂₆N₆O₈
• 分子量: 514.495
• InChiKey: SWPGIZSJNSZANV-RIURTTTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.74
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  183.99
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 N⁶-benzoyl-5'-deoxy-5'-(nitromethyl)-2',3'-O-isopropylideneadenosine 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 反应 0.5h， 以30%的产率得到N-{9-[(3aR,4R,6R,6aR)-6-(3-Hydroxy-1-hydroxymethyl-2-nitro-propyl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-yl}-benzamide
  参考文献：
  名称：

  Toward the synthesis of isozyme-specific enzyme inhibitors. Potent inhibitors of rat methionine adenosyltransferases. Effect of one-atom elongation of the ribose-P.alpha. bridge in two covalent adducts of L-methionine and .beta.,.gamma.-imido-ATP

  摘要：

  With 2',3'-O-isopropylideneadenosine or its N6-benzoyl derivative as starting material, synthetic routes to two novel adducts of L-methionine and beta,gamma-imido-ATP have been devised. One adduct, 14 (2:3 mixture of 6' epimers), had a P alpha OCH(R1)CH2 system [R1 = CH2-L-SCH2CH2CH2CH(NH2)CO2H] in place of the P alpha OC(5')H2 system of ATP, while the other, 16 (2:3 mixture of 5' epimers), had a P alpha OCH2CH2CH(R2) system [R2 = L-SCH2CH2CH(NH2)CO2H]. The ribose-P alpha bridge in 14 and 16 contained one more methylene group than in two homologous methionine-ATP adducts studied previously. Adduct 14 was a potent inhibitor of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase and gave competitive kinetics vs MgATP (Ki = 0.39 and 0.63 microM, respectively) or vs L-methionine (Ki = 2.2 and 2.7 microM). Adduct 16 was likewise a potent inhibitor competitive vs MgATP (Ki = 0.44 and 0.81 microM, respectively) or L-methionine (Ki = 2.1 and 1.5 microM). The kinetic data indicate that 14 and 16 inhibit by binding simultaneously to the MgATP and L-methionine substrate sites and that the extra methylene group facilitates the interaction of their methionine residues with these methionine sites.

  DOI：

  10.1021/jm00397a020