tert-butyl N-[(2S)-1-[[(2S)-1-[(3aR,6S,6aS)-6-(naphthalene-1-carbonylamino)-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate | 1131006-84-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl N-[(2S)-1-[[(2S)-1-[(3aR,6S,6aS)-6-(naphthalene-1-carbonylamino)-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate
• CAS: 1131006-84-2
• 化学式: C₃₃H₄₆N₄O₅
• 分子量: 578.752
• InChiKey: MWGFLCYZIIDAEJ-RKGCPJHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-1-[[(2S)-1-[(3aR,6S,6aS)-6-(naphthalene-1-carbonylamino)-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以43 mg的产率得到naphthalene-1-carboxylic acid {(3aR,6S,6aS)-1-[(S)-3,3-dimethyl-2-((S)-2-methylaminopropionylamino)butyryl]octahydrocyclopenta[b]pyrrol-6-yl}amide
  参考文献：
  名称：

  Orally Bioavailable Antagonists of Inhibitor of Apoptosis Proteins Based on an Azabicyclooctane Scaffold

  摘要：

  A series of IAP antagonists based on an azabicyclooctane scaffold was designed and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values of 140, 38, and 33 nM, respectively. These compounds promote degradation of c-IAP1, activate caspases, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Finally, compound 14b inhibits tumor growth when dosed orally in a breast cancer xenograft model.

  DOI：

  10.1021/jm801450c
• 作为产物：
  描述：

  {(S)-1-[(S)-1-((3aR,6S,6aS)-6-aminohexahydrocyclopenta[b]pyrrole-1-carbonyl)-2,2-dimethylpropylcarbamoyl]ethyl}methylcarbamic aid tert-butyl ester 、 1-萘甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以84 mg的产率得到tert-butyl N-[(2S)-1-[[(2S)-1-[(3aR,6S,6aS)-6-(naphthalene-1-carbonylamino)-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate
  参考文献：
  名称：

  Orally Bioavailable Antagonists of Inhibitor of Apoptosis Proteins Based on an Azabicyclooctane Scaffold

  摘要：

  A series of IAP antagonists based on an azabicyclooctane scaffold was designed and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values of 140, 38, and 33 nM, respectively. These compounds promote degradation of c-IAP1, activate caspases, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Finally, compound 14b inhibits tumor growth when dosed orally in a breast cancer xenograft model.

  DOI：

  10.1021/jm801450c