H-N-Me-Ala-Tle-Pro-(R)-tetrahydronaphth-1-yl amide hydrochloride | 845745-37-1

• 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: H-N-Me-Ala-Tle-Pro-(R)-tetrahydronaphth-1-yl amide hydrochloride
• 英文别名: (S)-1-((S)-3,3-Dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxamide hydrochloride；(2S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide;hydrochloride
• CAS: 845745-37-1
• 化学式: C₂₅H₃₈N₄O₃*ClH
• 分子量: 479.063
• InChiKey: CMFDULVBZVNDFI-RKVNAYBESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  90.5
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 palladium on activated charcoal 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 PS-carbodiimide resin 、 N,N-二甲基乙酰胺 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.16h， 生成 H-N-Me-Ala-Tle-Pro-(R)-tetrahydronaphth-1-yl amide hydrochloride
  参考文献：
  名称：

  Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer

  摘要：

  Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.

  DOI：

  10.1021/jm040037k