N-pyrazineformyl-3-naphth-2-ylalanine-L-phenylalanine | 1194235-15-8

• 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: N-pyrazineformyl-3-naphth-2-ylalanine-L-phenylalanine
• 英文别名: N-(2-pyrazinecarbonyl)-L-(2-naphthyl)-alanine-L-phenylalanine
• CAS: 1194235-15-8
• 化学式: C₂₇H₂₄N₄O₄
• 分子量: 468.512
• InChiKey: LUFIVRUSJXSVOJ-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.78
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  121.28
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-pyrazineformyl-3-naphth-2-ylalanine-L-phenylalanine 、 (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， 以87%的产率得到(+)-pinanediol N-(2-pyrazinecarbonyl)-L-(2-naphthyl)-alanine-L-phenylalanine-L-leucineboronate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of tripeptide boronic acid proteasome inhibitors

  摘要：

  A series of tripeptide boronate proteasome inhibitors were designed and synthesized on the basis of our previously built tripeptide aldehyde 3D-QSAR models. All the synthesized compounds were evaluated for their proteasome-inhibitory activities in an isolated 20S rabbit proteasome, and selected compounds were evaluated for their antitumor activities in vitro against four human cancer cell lines. Biological results showed bulky and negative substituents at P-2 position improved the proteasome-inhibitory potency obviously, which completely conformed to the theoretical models, while those at P-3 position thoroughly deviated from the 3D-QSAR model. Most of the screened compounds showed less than 1 nM inhibitory potency and high selectivity against 20S proteasome, of which 7f is the most potent (IC50 = 0.079 nM) and twofold more active than bortezomib (IC50 = 0.161 nM). Cell viability indicated hydrophilic 4-hydroxyphenyl substituent at P-2 or P-3 position was not favorable to the cellular activities. Especially for the two hematologic cancer cell lines, HL-60 and U266, 7f inhibited them at the level of less than 10 nM and was more potent than the control bortezomib. It is being considered a promising new lead to be developed for the treatment of various cancers. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.023
• 作为产物：
  描述：

  N-pyrazineformyl-3-naphth-2-ylalanyl-L-phenylalanine methyl ester 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 N-pyrazineformyl-3-naphth-2-ylalanine-L-phenylalanine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of tripeptide boronic acid proteasome inhibitors

  摘要：

  A series of tripeptide boronate proteasome inhibitors were designed and synthesized on the basis of our previously built tripeptide aldehyde 3D-QSAR models. All the synthesized compounds were evaluated for their proteasome-inhibitory activities in an isolated 20S rabbit proteasome, and selected compounds were evaluated for their antitumor activities in vitro against four human cancer cell lines. Biological results showed bulky and negative substituents at P-2 position improved the proteasome-inhibitory potency obviously, which completely conformed to the theoretical models, while those at P-3 position thoroughly deviated from the 3D-QSAR model. Most of the screened compounds showed less than 1 nM inhibitory potency and high selectivity against 20S proteasome, of which 7f is the most potent (IC50 = 0.079 nM) and twofold more active than bortezomib (IC50 = 0.161 nM). Cell viability indicated hydrophilic 4-hydroxyphenyl substituent at P-2 or P-3 position was not favorable to the cellular activities. Especially for the two hematologic cancer cell lines, HL-60 and U266, 7f inhibited them at the level of less than 10 nM and was more potent than the control bortezomib. It is being considered a promising new lead to be developed for the treatment of various cancers. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.023