(S)-2-[2-((R)-2-tert-Butoxycarbonylamino-4,4-dimethyl-pentanoylamino)-acetylamino]-3-(4-phenylethynyl-phenyl)-propionic acid methyl ester | 550376-97-1

• 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: (S)-2-[2-((R)-2-tert-Butoxycarbonylamino-4,4-dimethyl-pentanoylamino)-acetylamino]-3-(4-phenylethynyl-phenyl)-propionic acid methyl ester
• 英文别名: methyl (2S)-2-[[2-[[(2R)-4,4-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]acetyl]amino]-3-[4-(2-phenylethynyl)phenyl]propanoate
• CAS: 550376-97-1
• 化学式: C₃₂H₄₁N₃O₆
• 分子量: 563.694
• InChiKey: XFHGMYMTALJDQQ-IZZNHLLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-[2-((R)-2-tert-Butoxycarbonylamino-4,4-dimethyl-pentanoylamino)-acetylamino]-3-(4-phenylethynyl-phenyl)-propionic acid methyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 (S)-2-[2-((R)-2-Amino-4,4-dimethyl-pentanoylamino)-acetylamino]-3-(4-phenylethynyl-phenyl)-propionic acid methyl ester; hydrochloride
  参考文献：
  名称：

  Integrating Fragment Assembly and Biophysical Methods in the Chemical Advancement of Small-Molecule Antagonists of IL-2:  An Approach for Inhibiting Protein−Protein Interactions

  摘要：

  Fragment assembly has shown promise for discovering small-molecule antagonists for difficult targets, including protein-protein interactions. Here, we describe a process for identifying a 60 nM inhibitor of the interleukin-2 (IL-2)/IL-2 receptor (IL-2Ralpha) interaction. By use of fragment-based approaches, a compound with millimolar affinity was evolved to a hit series with low micromolar activity, and these compounds were optimized into a lead series with nanomolar affinity. Fragment assembly was useful not only for hit identification, but also for lead optimization. Throughout the discovery process, biophysical methods and structural biology demonstrated that compounds bound reversibly to IL-2 at the IL-2 receptor binding site.

  DOI：

  10.1021/jm049967u
• 作为产物：
  描述：

  (S)-2-amino-3-(4-phenylethynyl-phenyl)-propionic acid methyl ester hydrochloride 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.75h， 生成 (S)-2-[2-((R)-2-tert-Butoxycarbonylamino-4,4-dimethyl-pentanoylamino)-acetylamino]-3-(4-phenylethynyl-phenyl)-propionic acid methyl ester
  参考文献：
  名称：

  Integrating Fragment Assembly and Biophysical Methods in the Chemical Advancement of Small-Molecule Antagonists of IL-2:  An Approach for Inhibiting Protein−Protein Interactions

  摘要：

  Fragment assembly has shown promise for discovering small-molecule antagonists for difficult targets, including protein-protein interactions. Here, we describe a process for identifying a 60 nM inhibitor of the interleukin-2 (IL-2)/IL-2 receptor (IL-2Ralpha) interaction. By use of fragment-based approaches, a compound with millimolar affinity was evolved to a hit series with low micromolar activity, and these compounds were optimized into a lead series with nanomolar affinity. Fragment assembly was useful not only for hit identification, but also for lead optimization. Throughout the discovery process, biophysical methods and structural biology demonstrated that compounds bound reversibly to IL-2 at the IL-2 receptor binding site.

  DOI：

  10.1021/jm049967u