2,2,2-trichloroethyl N-2-[S-methylsulfonimidoyl]ethylcarbamate | 1401207-25-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: 2,2,2-trichloroethyl N-2-[S-methylsulfonimidoyl]ethylcarbamate
• CAS: 1401207-25-7
• 化学式: C₆H₁₁Cl₃N₂O₃S
• 分子量: 297.59
• InChiKey: WQZMOOPIVMTWKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  15.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  79.25
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,2,2-trichloroethyl N-2-[S-methylsulfonimidoyl]ethylcarbamate 在 四氮唑 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.5h， 生成 2,2,2-trichloroethyl 2-{N-[hydroxy(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphoryl]-S-methyl-(R,S)-sulfonimidoyl}ethylcarbamate morpholine salt
  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
• 作为产物：
  描述：

  2,2,2-trichloroethyl N-2-[S-methylsulfinyl]ethylcarbamate 在 2,4,6-三甲基苯磺酰羟胺 作用下， 以 乙腈 为溶剂， 反应 96.0h， 以65%的产率得到2,2,2-trichloroethyl N-2-[S-methylsulfonimidoyl]ethylcarbamate
  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