(R)-1-[(R)-3-benzamido-3-(4-methoxyphenyl)-propanamido]-3-methylbutylboronic acid pinanediol ester | 1215875-91-4

• 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: (R)-1-[(R)-3-benzamido-3-(4-methoxyphenyl)-propanamido]-3-methylbutylboronic acid pinanediol ester
• CAS: 1215875-91-4
• 化学式: C₃₂H₄₃BN₂O₅
• 分子量: 546.515
• InChiKey: VPCKCSDDZHZRNF-AKTGGBSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.35
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  85.89
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-1-[(R)-3-benzamido-3-(4-methoxyphenyl)-propanamido]-3-methylbutylboronic acid pinanediol ester 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0.232 g的产率得到(1R)-1-[(3R)-3-benzamido-3-(4-methoxyphenyl)propanamido]-3-methylbutylboronic 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
• 作为产物：
  描述：

  (R)-3-benzamido-3-(4-methoxyphenyl)propanoic acid 、 (R)-1-氨基-3-甲基丁基硼酸蒎烷二醇酯盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.33h， 生成 (R)-1-[(R)-3-benzamido-3-(4-methoxyphenyl)-propanamido]-3-methylbutylboronic acid pinanediol ester
  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