(S)-N-((S)-2-((S)-1-benzylpyrrolidin-3-ylamino)-1-cyclohexyl-2-oxoethyl)-2-(methylamino)propanamide | 1361322-42-0

• 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)-N-((S)-2-((S)-1-benzylpyrrolidin-3-ylamino)-1-cyclohexyl-2-oxoethyl)-2-(methylamino)propanamide
• 英文别名: (2S)-N-[(1S)-2-[[(3S)-1-benzylpyrrolidin-3-yl]amino]-1-cyclohexyl-2-oxoethyl]-2-(methylamino)propanamide
• CAS: 1361322-42-0
• 化学式: C₂₃H₃₆N₄O₂
• 分子量: 400.564
• InChiKey: OIKYOABFOPRPEZ-YYWHXJBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  73.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-benzyl 3-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-2-cyclohexylacetamido)pyrrolidine-1-carboxylate 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 (S)-N-((S)-2-((S)-1-benzylpyrrolidin-3-ylamino)-1-cyclohexyl-2-oxoethyl)-2-(methylamino)propanamide
  参考文献：
  名称：

  Discovery of aminopiperidine-based Smac mimetics as IAP antagonists

  摘要：

  A series of structurally unique Smac mimetics that act as antagonists of inhibitor of apoptosis proteins (IAPs) has been discovered. While most previously described Smac mimetics contain the proline ring (or a similar cyclic motif) found in Smac, a key feature of the compounds described herein is that this ring has been removed. Despite this, compounds in this series potently bind to cIAP1 and elicit the expected phenotype of cIAP1 inhibition in cancer cells. Marked selectivity for cIAP1 over XIAP is observed for these compounds, which is attributed to a slight difference in the binding groove between the two proteins and the resulting steric interactions with the inhibitors. XIAP binding can be improved by constraining the inhibitor so that these unfavorable steric interactions are minimized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.109

文献信息

• Discovery of aminopiperidine-based Smac mimetics as IAP antagonists
  作者：Edward J. Hennessy、Jamal C. Saeh、Li Sha、Terry MacIntyre、Haiyun Wang、Nicholas A. Larsen、Brian M. Aquila、Andrew D. Ferguson、Naomi M. Laing、Charles A. Omer

  DOI：10.1016/j.bmcl.2011.12.109

  日期：2012.2

  A series of structurally unique Smac mimetics that act as antagonists of inhibitor of apoptosis proteins (IAPs) has been discovered. While most previously described Smac mimetics contain the proline ring (or a similar cyclic motif) found in Smac, a key feature of the compounds described herein is that this ring has been removed. Despite this, compounds in this series potently bind to cIAP1 and elicit the expected phenotype of cIAP1 inhibition in cancer cells. Marked selectivity for cIAP1 over XIAP is observed for these compounds, which is attributed to a slight difference in the binding groove between the two proteins and the resulting steric interactions with the inhibitors. XIAP binding can be improved by constraining the inhibitor so that these unfavorable steric interactions are minimized. (C) 2011 Elsevier Ltd. All rights reserved.