2-aminoethyl [S-methylsulfonimidoyl]-N-adenylate | 1401207-21-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-aminoethyl [S-methylsulfonimidoyl]-N-adenylate
• 英文别名: N-(2-aminoethyl-methyl-oxo-lambda6-sulfanylidene)-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]phosphonamidic acid；N-(2-aminoethyl-methyl-oxo-λ6-sulfanylidene)-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]phosphonamidic acid
• CAS: 1401207-21-3
• 化学式: C₁₃H₂₂N₇O₇PS
• 分子量: 451.4
• InChiKey: QGAWKHHHZNADQH-MQJQZHHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  230
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2,2,2-trichloroethyl 2-{N-[(allyloxy)(2',3'-O-isopropylideneadenosin-5'-yloxy)-(R,S)-phosphoryl]-S-methyl-(R,S)-sulfonimidoyl}ethylcarbamate 在 四(三苯基膦)钯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 2-aminoethyl [S-methylsulfonimidoyl]-N-adenylate
  参考文献：
  名称：

  A sulfoximine-based inhibitor of human asparagine synthetase kills l-asparaginase-resistant leukemia cells

  摘要：

  An adenylated sulfoximine transition-state analogue 1, which inhibits human asparagine synthetase (hASNS) with nanomolar potency, has been reported to suppress the proliferation of an L-asparagine amidohydrolase (ASNase)-resistant MOLT-4 leukemia cell line (MOLT-4R) when L-asparagine is depleted in the medium. We now report the synthesis and biological activity of two new sulfoximine analogues of 1 that have been studied as part of systematic efforts to identify compounds with improved cell permeability and/or metabolic stability. One of these new analogues, an amino sulfoximine 5 having no net charge at cellular pH, is a better hASNS inhibitor (K*(I) = 8 nM) than 1 and suppresses proliferation of MOLT-4R cells at 10-fold lower concentration (IC50 = 0.1 mM). More importantly, and in contrast to the lead compound 1, the presence of sulfoximine 5 at concentrations above 0.25 mM causes the death of MOLT-4R cells even when ASNase is absent in the culture medium. The amino sulfoximine 5 exhibits different dose-response behavior when incubated with an ASNase-sensitive MOLT-4 cell line (MOLT-4S), supporting the hypothesis that sulfoximine 5 exerts its effect by inhibiting hASNS in the cell. Our work provides further evidence for the idea that hASNS represents a chemotherapeutic target for the treatment of leukemia, and perhaps other cancers, including those of the prostate. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.047