N1-(2-(diethylamino)ethyl)-N4-((S)-4-methyl-1-((S)-4-methyl-1-((S,E)-5-methyl-1-(methylsulfonyl)hex-1-en-3-ylamino)-1-oxopentan-2-ylamino)-1-oxopentan-2-yl)terephthalamide | 1346804-68-9

• 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: N1-(2-(diethylamino)ethyl)-N4-((S)-4-methyl-1-((S)-4-methyl-1-((S,E)-5-methyl-1-(methylsulfonyl)hex-1-en-3-ylamino)-1-oxopentan-2-ylamino)-1-oxopentan-2-yl)terephthalamide
• 英文别名: 1-N-[2-(diethylamino)ethyl]-4-N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(E,3S)-5-methyl-1-methylsulfonylhex-1-en-3-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]benzene-1,4-dicarboxamide
• CAS: 1346804-68-9
• 化学式: C₃₄H₅₇N₅O₆S
• 分子量: 663.922
• InChiKey: YSWVFAAITRJIKI-XVYWTRDJSA-N

物化性质

• 熔点：
  102 °C
• 沸点：
  909.3±65.0 °C(predicted)
• 密度：
  1.102±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  46
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(2-Diethylamino-ethyl)-N'-{(S)-1-[(S)-1-((S)-1-formyl-3-methyl-butylcarbamoyl)-3-methyl-butylcarbamoyl]-3-methyl-butyl}-terephthalamide 、 二乙基(甲基磺酰基)膦 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 0.5h， 以42%的产率得到N1-(2-(diethylamino)ethyl)-N4-((S)-4-methyl-1-((S)-4-methyl-1-((S,E)-5-methyl-1-(methylsulfonyl)hex-1-en-3-ylamino)-1-oxopentan-2-ylamino)-1-oxopentan-2-yl)terephthalamide
  参考文献：
  名称：

  New aldehyde and vinylsulfone proteasome inhibitors for targeted melanoma therapy

  摘要：

  The proteasome is a promising target in cancer therapy. However, it is ubiquitous and its inhibitors cause side effects. To target melanoma cells we synthesized new peptide aldehyde and vinylsulfone inhibitors of the proteasome conjugated to the melanin-targeting ligand (MTL) derived from radiotracer [I-123]-N-(2-diethylaminoethyl)benzamide ([I-123]BZA) or [I-125]-N-(4-dipropylaminobutyl)-4-iodobenzamide ([I-125] BZ18). Influence on the cytotoxicity of the benzamide alkyl side chain length and the composition of the amino acid sequence was assessed. Among the conjugates evaluated, compound 16 and 22 presented the highest cytotoxicity (IC50, 0.71 and 0.64 mu M respectively), which persisted in the presence of an MTL derived from N-(dialkylaminoalkylenyl)benzamide residue. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.07.037

文献信息

• New aldehyde and vinylsulfone proteasome inhibitors for targeted melanoma therapy
  作者：Magali Vivier、Maryse Rapp、Marie-Josephe Galmier、Anne-Sophie Jarrousse、Elisabeth Miot-Noirault、Fernand Leal、Valérie Weber、Jacques Métin、Jacques Sauzière、Jean-Michel Chezal、Jean-Claude Madelmont

  DOI：10.1016/j.ejmech.2011.07.037

  日期：2011.11

  The proteasome is a promising target in cancer therapy. However, it is ubiquitous and its inhibitors cause side effects. To target melanoma cells we synthesized new peptide aldehyde and vinylsulfone inhibitors of the proteasome conjugated to the melanin-targeting ligand (MTL) derived from radiotracer [I-123]-N-(2-diethylaminoethyl)benzamide ([I-123]BZA) or [I-125]-N-(4-dipropylaminobutyl)-4-iodobenzamide ([I-125] BZ18). Influence on the cytotoxicity of the benzamide alkyl side chain length and the composition of the amino acid sequence was assessed. Among the conjugates evaluated, compound 16 and 22 presented the highest cytotoxicity (IC50, 0.71 and 0.64 mu M respectively), which persisted in the presence of an MTL derived from N-(dialkylaminoalkylenyl)benzamide residue. (C) 2011 Elsevier Masson SAS. All rights reserved.