3-(3-chlorophenyl)-3-[(S)-1,2,3,4-tetrahydronaphthalene-1-carboxamido]propanoic acid | 1257212-59-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(3-chlorophenyl)-3-[(S)-1,2,3,4-tetrahydronaphthalene-1-carboxamido]propanoic acid
• 英文别名: 3-(3-chlorophenyl)-3-[[(1S)-1,2,3,4-tetrahydronaphthalene-1-carbonyl]amino]propanoic acid
• CAS: 1257212-59-1
• 化学式: C₂₀H₂₀ClNO₃
• 分子量: 357.837
• InChiKey: LPPIZKKVSCGSNL-ZENAZSQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨基-3-(3-氯苯基)丙酸甲酯 在 水 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氯化碳 、 丙酮 为溶剂， 生成 3-(3-chlorophenyl)-3-[(S)-1,2,3,4-tetrahydronaphthalene-1-carboxamido]propanoic acid
  参考文献：
  名称：

  Synthesis, in Vitro and in Vivo Biological Evaluation, and Comprehensive Understanding of Structure−Activity Relationships of Dipeptidyl Boronic Acid Proteasome Inhibitors Constructed from β-Amino Acids

  摘要：

  An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids is reported. SAR analysis revealed that bicyclic groups at the RI position, 3-F substituents at the R-2 position, and bulky aliphatic groups at the R-3 position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 mu M. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.

  DOI：

  10.1021/jm1009742

文献信息

• Synthesis, in Vitro and in Vivo Biological Evaluation, and Comprehensive Understanding of Structure−Activity Relationships of Dipeptidyl Boronic Acid Proteasome Inhibitors Constructed from β-Amino Acids
  作者：Yongqiang Zhu、Gang Wu、Xinrong Zhu、Yuheng Ma、Xin Zhao、Yuejie Li、Yunxia Yuan、Jie Yang、Sen Yu、Feng Shao、Meng Lei

  DOI：10.1021/jm1009742

  日期：2010.12.23

  An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids is reported. SAR analysis revealed that bicyclic groups at the RI position, 3-F substituents at the R-2 position, and bulky aliphatic groups at the R-3 position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 mu M. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.