[(1S)-1-[[(2S)-3-phenyl-2-[((S)-(-)-1,2,3,4-tetrahydro-naphthoic-1-carbonyl)amino]-1-oxopropyl]amino]-3-methylbutyl]boronic acid | 1173166-90-9

• 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: [(1S)-1-[[(2S)-3-phenyl-2-[((S)-(-)-1,2,3,4-tetrahydro-naphthoic-1-carbonyl)amino]-1-oxopropyl]amino]-3-methylbutyl]boronic acid
• 英文别名: [(1S)-3-methyl-1-[[(2S)-3-phenyl-2-[[(1S)-1,2,3,4-tetrahydronaphthalene-1-carbonyl]amino]propanoyl]amino]butyl]boronic acid
• CAS: 1173166-90-9
• 化学式: C₂₅H₃₃BN₂O₄
• 分子量: 436.359
• InChiKey: HLDAUCRRBXUURL-RJGXRXQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.38
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  98.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-[(1S)-1-[[[(1S)-1-[(3aR,4R,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborol-2-yl]-3-methylbutyl]amino]carbonyl]-2-phenyl]-1-(S)-(-)-1,2,3,4-tetrahydro-naphthoiccarboxamide 在 盐酸 、 异丁基硼酸 、 水 作用下， 以 甲醇 、 正己烷 为溶剂， 反应 18.0h， 生成 [(1S)-1-[[(2S)-3-phenyl-2-[((S)-(-)-1,2,3,4-tetrahydro-naphthoic-1-carbonyl)amino]-1-oxopropyl]amino]-3-methylbutyl]boronic acid
  参考文献：
  名称：

  Design, Synthesis, Biological Evaluation, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronate Proteasome Inhibitors, Part I: Comprehensive Understanding of the SAR of α-Amino Acid Boronates

  摘要：

  New series of dipeptidyl boronate inhibitors of 20S proteasome were designed and synthesized, The comprehensive understanding or the SAR was obtained by utilizing the variation of four substituents. From the screened compounds in enzyme, novel inhibitors 49 and 50 were identified to be highly potent druglike candidates with IC50 values of 1.2 and 1.6 nM, respectively, which showed better activities than the drug bortezomib on the market. Two hematologic human tumor cell lines, HL-60 and U266, were significantly sensitive to both candidates and showed nearly the same potency as the standard bortezomib with IC50 values less than 10 nM. But as for most of the eight human solid tumor cell lines, both candidates were more potent than the standard with the IC50 value range of 9.8-70 nM. The activity evaluation of the stereoisomers showed that changing R-isomers to S-isomers greatly reduced the potency and even induced inactivity.

  DOI：

  10.1021/jm9005093

文献信息

• Design, Synthesis, Biological Evaluation, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronate Proteasome Inhibitors, Part I: Comprehensive Understanding of the SAR of α-Amino Acid Boronates
  作者：Yongqiang Zhu、Xin Zhao、Xinrong Zhu、Gang Wu、Yuejie Li、Yuheng Ma、Yunxia Yuan、Jie Yang、Yang Hu、Li Ai、Qingzhi Gao

  DOI：10.1021/jm9005093

  日期：2009.7.23

  New series of dipeptidyl boronate inhibitors of 20S proteasome were designed and synthesized, The comprehensive understanding or the SAR was obtained by utilizing the variation of four substituents. From the screened compounds in enzyme, novel inhibitors 49 and 50 were identified to be highly potent druglike candidates with IC50 values of 1.2 and 1.6 nM, respectively, which showed better activities than the drug bortezomib on the market. Two hematologic human tumor cell lines, HL-60 and U266, were significantly sensitive to both candidates and showed nearly the same potency as the standard bortezomib with IC50 values less than 10 nM. But as for most of the eight human solid tumor cell lines, both candidates were more potent than the standard with the IC50 value range of 9.8-70 nM. The activity evaluation of the stereoisomers showed that changing R-isomers to S-isomers greatly reduced the potency and even induced inactivity.