(1R)-1-(L-O-methyltyrosyl-L-valyl)amino-2-(4-methylphenyl)-ethylboronic acid hydrochloride | 1158975-01-9

• 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: (1R)-1-(L-O-methyltyrosyl-L-valyl)amino-2-(4-methylphenyl)-ethylboronic acid hydrochloride
• 英文别名: [(1R)-1-[[(2S)-2-[[(2S)-2-amino-3-(4-methoxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-2-(4-methoxyphenyl)ethyl]boronic acid;hydrochloride
• CAS: 1158975-01-9
• 化学式: C₂₄H₃₄BN₃O₆*ClH
• 分子量: 507.822
• InChiKey: AXVXUOOVNMPSQF-SGIIKHNDSA-N

物化性质

• 熔点：
  162-164 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.88
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  143
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-氯吡啶-2-羧酸 、 (1R)-1-(L-O-methyltyrosyl-L-valyl)amino-2-(4-methylphenyl)-ethylboronic acid hydrochloride 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， 生成 [(1R)-1-[[(2S)-2-[[(2S)-2-[(6-chloropyridine-2-carbonyl)amino]-3-(4-methoxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-2-(4-methoxyphenyl)ethyl]boronic acid
  参考文献：
  名称：

  酪肽的硼酸衍生物的结构-活性关系：蛋白酶体抑制剂

  摘要：

  研究了蛋白酶体抑制剂tyropeptin的硼酸衍生物的结构-活性关系。基于先前报道的酪肽素（2）的硼酸酯类似物的结构，合成了在N-末端酰基部分和P2位置具有不同亚结构的41种衍生物。其中3-苯氧基苯基乙酰胺6和3-氟吡啶甲酰胺22分别对蛋白酶体的胰凝乳蛋白酶活性和细胞毒性表现出最强的抑制活性。将P2侧链中的异丙基替换为H或Me对本研究中检测到的生物学活性的影响可忽略不计。

  DOI：

  10.1016/j.bmcl.2010.07.122
• 作为产物：
  描述：

  在 盐酸 、 异丁基硼酸 、 水 作用下， 以 正己烷 为溶剂， 反应 1.0h， 以88.2 mg的产率得到(1R)-1-(L-O-methyltyrosyl-L-valyl)amino-2-(4-methylphenyl)-ethylboronic acid hydrochloride
  参考文献：
  名称：

  Synthesis of boronic acid derivatives of tyropeptin: Proteasome inhibitors

  摘要：

  Boronic acid derivatives of tyropeptin were synthesized with TP-110 as the lead compound. Due to the lability of the aminoboronic acid moiety, careful design of the deprotection and coupling sequence was required. Liquid-liquid partition chromatography was found to be a powerful tool for purification of compounds of this class. The obtained derivatives showed potent inhibitory activities against the human 20S proteasome in vitro. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.117

文献信息

• Structure–activity relationship of boronic acid derivatives of tyropeptin: Proteasome inhibitors
  作者：Takumi Watanabe、Hikaru Abe、Isao Momose、Yoshikazu Takahashi、Daishiro Ikeda、Yuzuru Akamatsu

  DOI：10.1016/j.bmcl.2010.07.122

  日期：2010.10

  of the boronic acid derivatives of tyropeptin, a proteasome inhibitor, was studied. Based on the structure of a previously reported boronate analog of tyropeptin (2), 41 derivatives, which have varying substructure at the N-terminal acyl moiety and P2 position, were synthesized. Among them, 3-phenoxyphenylacetamide 6 and 3-fluoro picolinamide 22 displayed the most potent inhibitory activity toward

  研究了蛋白酶体抑制剂tyropeptin的硼酸衍生物的结构-活性关系。基于先前报道的酪肽素（2）的硼酸酯类似物的结构，合成了在N-末端酰基部分和P2位置具有不同亚结构的41种衍生物。其中3-苯氧基苯基乙酰胺6和3-氟吡啶甲酰胺22分别对蛋白酶体的胰凝乳蛋白酶活性和细胞毒性表现出最强的抑制活性。将P2侧链中的异丙基替换为H或Me对本研究中检测到的生物学活性的影响可忽略不计。
• Synthesis of boronic acid derivatives of tyropeptin: Proteasome inhibitors
  作者：Takumi Watanabe、Isao Momose、Masatoshi Abe、Hikaru Abe、Ryuichi Sawa、Yoji Umezawa、Daishiro Ikeda、Yoshikazu Takahashi、Yuzuru Akamatsu

  DOI：10.1016/j.bmcl.2009.02.117

  日期：2009.4

  Boronic acid derivatives of tyropeptin were synthesized with TP-110 as the lead compound. Due to the lability of the aminoboronic acid moiety, careful design of the deprotection and coupling sequence was required. Liquid-liquid partition chromatography was found to be a powerful tool for purification of compounds of this class. The obtained derivatives showed potent inhibitory activities against the human 20S proteasome in vitro. (C) 2009 Elsevier Ltd. All rights reserved.