allyl 3-{N-[(allyloxy)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphoryl]-S-methylsulfonimidoyl}propanoate | 1401207-30-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: allyl 3-{N-[(allyloxy)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphoryl]-S-methylsulfonimidoyl}propanoate
• CAS: 1401207-30-4
• 化学式: C₂₃H₃₃N₆O₉PS
• 分子量: 600.59
• InChiKey: VSWNTVPOPRLRTD-VNGAADECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.37
• 重原子数：
  40.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  188.57
• 氢给体数：
  1.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  吗啉 、 allyl 3-{N-[(allyloxy)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphoryl]-S-methylsulfonimidoyl}propanoate 在 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 以1.33 g的产率得到3-{N-[(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphoryl]-S-methylsulfonimidoyl}propanoic acid bis-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-propen-1-yl 3-(methylthio)propanoate 在 四氮唑 、 sodium periodate 、 2,4,6-三甲基苯磺酰羟胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 98.0h， 生成 allyl 3-{N-[(allyloxy)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphoryl]-S-methylsulfonimidoyl}propanoate
  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