(R)-1-[3-nicotinamido-3-(4-methoxyphenyl)propan-amido]-3-methylbutyl boronic acid | 1215876-22-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-1-[3-nicotinamido-3-(4-methoxyphenyl)propan-amido]-3-methylbutyl boronic acid
• 英文别名: [(1R)-1-[[3-(4-methoxyphenyl)-3-(pyridine-3-carbonylamino)propanoyl]amino]-3-methylbutyl]boronic acid
• CAS: 1215876-22-4
• 化学式: C₂₁H₂₈BN₃O₅
• 分子量: 413.281
• InChiKey: IQXGJRIAFNXLHT-GGYWPGCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.49
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  pinanediol ester (R)-1-[3-nicotinamido-3-(4-methoxyphenyl)propan-amido]-3-methylbutyl boronic acid 在 盐酸 、 异丁基硼酸 、 水 、 碳酸氢钠 作用下， 以 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 18.0h， 以0.18 g的产率得到(R)-1-[3-nicotinamido-3-(4-methoxyphenyl)propan-amido]-3-methylbutyl boronic acid
  参考文献：
  名称：

  Synthesis, in Vitro and in Vivo Biological Evaluation, Docking Studies, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronic Acid Proteasome Inhibitors Composed of β-Amino Acids

  摘要：

  A series of novel dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i wits the most active. The IC50 value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active its the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC50 values nearly less than 5 mu M against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in it similar way as bortezomib.

  DOI：

  10.1021/jm901407s

文献信息

• Synthesis, in Vitro and in Vivo Biological Evaluation, Docking Studies, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronic Acid Proteasome Inhibitors Composed of β-Amino Acids
  作者：Yongqiang Zhu、Xinrong Zhu、Gang Wu、Yuheng Ma、Yuejie Li、Xin Zhao、Yunxia Yuan、Jie Yang、Sen Yu、Feng Shao、Runtao Li、Yanrong Ke、Aijun Lu、Zhenming Liu、Liangren Zhang

  DOI：10.1021/jm901407s

  日期：2010.3.11

  A series of novel dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i wits the most active. The IC50 value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active its the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC50 values nearly less than 5 mu M against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in it similar way as bortezomib.