[(1S)-(2-hydroxyethyl)-2-oxohex-5-enyl]carbamic acid tert-butyl ester | 926895-66-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(1S)-(2-hydroxyethyl)-2-oxohex-5-enyl]carbamic acid tert-butyl ester
• CAS: 926895-66-1
• 化学式: C₁₃H₂₃NO₄
• 分子量: 257.33
• InChiKey: DRENTYSSJVMLEH-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  75.63
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [(1S)-(2-hydroxyethyl)-2-oxohex-5-enyl]carbamic acid tert-butyl ester 在 重铬酸吡啶 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 (3S)-tert-butoxycarbonylamino-4-oxooct-7-enoic acid benzyl ester
  参考文献：
  名称：

  Inhibition of P-glycoprotein-mediated multidrug efflux by aminomethylene and ketomethylene analogs of reversins

  摘要：

  Several aminomethylene analogs and a ketomethylene analog of reversins were synthesized in order to evaluate their ability to inhibit P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein. These analogs retained good activity compared to cyclosporin A and the original reversins. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.059
• 作为产物：
  描述：

  {(1S)-[2-(tert-butyldimethylsilanyloxy)ethyl]-2-oxohex-5-enyl}carbamic acid tert-butyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以87%的产率得到[(1S)-(2-hydroxyethyl)-2-oxohex-5-enyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of P-glycoprotein-mediated multidrug efflux by aminomethylene and ketomethylene analogs of reversins

  摘要：

  Several aminomethylene analogs and a ketomethylene analog of reversins were synthesized in order to evaluate their ability to inhibit P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein. These analogs retained good activity compared to cyclosporin A and the original reversins. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.059

文献信息

• Potent and Fully Noncompetitive Peptidomimetic Inhibitor of Multidrug Resistance P-Glycoprotein
  作者：Ophélie Arnaud、Ali Koubeissi、Laurent Ettouati、Raphaël Terreux、Ghina Alamé、Catherine Grenot、Charles Dumontet、Attilio Di Pietro、Joëlle Paris、Pierre Falson

  DOI：10.1021/jm100839w

  日期：2010.9.23

  N-alpha-Boc-L-Asp(OBn)-L-Lys(Z)-OtBu (reversin 121, I), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-L-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (1050) of 0.6 and 0.2 mu M, which are 2- and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the and R drug-transport sites.