N-pyrazineformyl-L-phenylalanyl-L-tyrosine | 1194235-16-9

• 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: N-pyrazineformyl-L-phenylalanyl-L-tyrosine
• 英文别名: N-(2-pyrazinecarbonyl)-L-phenylalanine-L-tyrosine；pyrazinoyl-Phe-Tyr-OH；(2S)-3-(4-hydroxyphenyl)-2-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]propanoic acid
• CAS: 1194235-16-9
• 化学式: C₂₃H₂₂N₄O₅
• 分子量: 434.451
• InChiKey: GZEMOWZRCQMLIF-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  142
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-pyrazineformyl-L-phenylalanyl-L-tyrosine 、 (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81%的产率得到(+)-pinanediol N-(2-pyrazinecarbonyl)-L-phenylalanine-L-tyrosine-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-L-phenylalanyl-L-tyrosine methyl ester 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 N-pyrazineformyl-L-phenylalanyl-L-tyrosine
  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

文献信息

• TRIPETIDE BORONIC ACID OR BORONIC ESTER, PREPARATIVE METHOD AND USE THEREOF
  申请人：Li Runtao

  公开号：US20120135921A1

  公开（公告）日：2012-05-31

  The present invention discloses proteasome inhibitors of tripeptide boronic acids or boronic esters represented by Formula (I), preparative method and use thereof. The proteasome inhibitors are therapeutical agents for treating malignant tumor, various nervous system degenerative diseases, muscle cachexia or diabetes, wherein the malignant tumor is leukemia, gastric cancer, hepatocarcinoma or nasopharyngeal carcinoma.

  本发明公开了由式（I）所表示的三肽硼酸或硼酯的蛋白酶抑制剂，其制备方法及用途。这些蛋白酶抑制剂是用于治疗恶性肿瘤、各种神经系统退行性疾病、肌肉消耗症或糖尿病的治疗剂，其中恶性肿瘤是白血病、胃癌、肝癌或鼻咽癌。
• TRIPEPTIDE BORONIC ACID OR BORONIC ESTER, PREPARATIVE METHOD AND USE THEREOF
  申请人：Peking University

  公开号：EP2444411B1

  公开（公告）日：2016-10-26
• US9421237B2
  申请人：——

  公开号：US9421237B2

  公开（公告）日：2016-08-23
• Design, synthesis and biological evaluation of tripeptide boronic acid proteasome inhibitors
  作者：Yongqiang Zhu、Shuyang Yao、Bo Xu、Zemei Ge、Jingrong Cui、Tieming Cheng、Runtao Li

  DOI：10.1016/j.bmc.2009.08.023

  日期：2009.10

  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.