2-oxo-(3S)-[(tert-butyloxy)carbonylamino]-4-[(4-tert-butyloxy)phenyl]butyl phenyl sulfone | 244047-96-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-oxo-(3S)-[(tert-butyloxy)carbonylamino]-4-[(4-tert-butyloxy)phenyl]butyl phenyl sulfone
• 英文别名: tert-butyl N-[(2S)-4-(benzenesulfonyl)-1-[4-[(2-methylpropan-2-yl)oxy]phenyl]-3-oxobutan-2-yl]carbamate
• CAS: 244047-96-9
• 化学式: C₂₅H₃₃NO₆S
• 分子量: 475.606
• InChiKey: JUOHOBLXVYDWBR-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-oxo-(3S)-[(tert-butyloxy)carbonylamino]-4-[(4-tert-butyloxy)phenyl]butyl phenyl sulfone 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 disodium hydrogenphosphate 、 sodium amalgam 、 potassium carbonate 作用下， 以 吡啶 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (E)-(S)-5-tert-Butoxycarbonylamino-6-(4-tert-butoxy-phenyl)-hex-3-enoic acid tert-butyl ester
  参考文献：
  名称：

  New application of the Julia olefination for the synthesis of Tyr-Gly E-alkene and carba isostere pseudopeptides

  摘要：

  A new application of the Julia olefination to the synthesis of Tyr Psi[E-CH=CH]Gly and Tyr Psi[CH2CH2]Gly pseudopeptides is described via condensation of tertiobutyl bromoacetate on tyrosine-derived beta-ketosulfone and subsequent reductive desulfonation. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)01139-9
• 作为产物：
  描述：

  苯甲砜 、 Boc-L-Tyr(tBu)-OMe 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以71%的产率得到2-oxo-(3S)-[(tert-butyloxy)carbonylamino]-4-[(4-tert-butyloxy)phenyl]butyl phenyl sulfone
  参考文献：
  名称：

  Potent and Fully Noncompetitive Peptidomimetic Inhibitor of Multidrug Resistance P-Glycoprotein

  摘要：

  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.

  DOI：

  10.1021/jm100839w

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.
• New application of the Julia olefination for the synthesis of Tyr-Gly E-alkene and carba isostere pseudopeptides
  作者：Cécile Charrier、Laurent Ettouati、Joelle Paris

  DOI：10.1016/s0040-4039(99)01139-9

  日期：1999.7

  A new application of the Julia olefination to the synthesis of Tyr Psi[E-CH=CH]Gly and Tyr Psi[CH2CH2]Gly pseudopeptides is described via condensation of tertiobutyl bromoacetate on tyrosine-derived beta-ketosulfone and subsequent reductive desulfonation. (C) 1999 Elsevier Science Ltd. All rights reserved.