tert-butyl methyl ((S)-1-(((5S,8S,10aR)-3-(3-methylbutanoyl)-6-oxo-8-(((R)-1-phenylprop-2-yn-1-yl)carbamoyl)decahydropyrrolo[1,2-a][ 1,5]-diazocin-5-yl)amino)-1-oxopropan-2-yl)carbamate | 1290536-81-0

• 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: tert-butyl methyl ((S)-1-(((5S,8S,10aR)-3-(3-methylbutanoyl)-6-oxo-8-(((R)-1-phenylprop-2-yn-1-yl)carbamoyl)decahydropyrrolo[1,2-a][ 1,5]-diazocin-5-yl)amino)-1-oxopropan-2-yl)carbamate
• 英文别名: tert-butyl N-[(2S)-1-[[(5S,8S,10aR)-3-(3-methylbutanoyl)-6-oxo-8-[[(1R)-1-phenylprop-2-ynyl]carbamoyl]-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate
• CAS: 1290536-81-0
• 化学式: C₃₃H₄₇N₅O₆
• 分子量: 609.766
• InChiKey: URVJRKUMPKAALC-OLZHSIAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl methyl ((S)-1-(((5S,8S,10aR)-3-(3-methylbutanoyl)-6-oxo-8-(((R)-1-phenylprop-2-yn-1-yl)carbamoyl)decahydropyrrolo[1,2-a][ 1,5]-diazocin-5-yl)amino)-1-oxopropan-2-yl)carbamate 在 palladium 10% on activated carbon 、 氢气 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 甲醇 、 水 、 乙腈 、 叔丁醇 为溶剂， 生成 tert-butyl N-[(2S)-1-[[(5S,8S,10aR)-8-[[(S)-[1-(10-aminodecyl)triazol-4-yl]-phenylmethyl]carbamoyl]-3-(3-methylbutanoyl)-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate
  参考文献：
  名称：

  A Potent and Orally Active Antagonist (SM-406/AT-406) of Multiple Inhibitor of Apoptosis Proteins (IAPs) in Clinical Development for Cancer Treatment

  摘要：

  We report the discovery and characterization of SM-406 (compound 2), a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). This compound binds to XIAP, cIAP1, and cIAP2 proteins with K(i) of 66.4, 1.9, and 5.1 nM, respectively. Compound 2 effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Compound 2 is currently in phase I clinical trials for the treatment of human cancer.

  DOI：

  10.1021/jm101505d
• 作为产物：
  描述：

  (5S,8S,10aR)-methyl 5-(tert-butoxycarbonylamino)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxylate 在 盐酸 、 甲醇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 tert-butyl methyl ((S)-1-(((5S,8S,10aR)-3-(3-methylbutanoyl)-6-oxo-8-(((R)-1-phenylprop-2-yn-1-yl)carbamoyl)decahydropyrrolo[1,2-a][ 1,5]-diazocin-5-yl)amino)-1-oxopropan-2-yl)carbamate
  参考文献：
  名称：

  A Potent and Orally Active Antagonist (SM-406/AT-406) of Multiple Inhibitor of Apoptosis Proteins (IAPs) in Clinical Development for Cancer Treatment

  摘要：

  We report the discovery and characterization of SM-406 (compound 2), a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). This compound binds to XIAP, cIAP1, and cIAP2 proteins with K(i) of 66.4, 1.9, and 5.1 nM, respectively. Compound 2 effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Compound 2 is currently in phase I clinical trials for the treatment of human cancer.

  DOI：

  10.1021/jm101505d

文献信息

• A Potent and Orally Active Antagonist (SM-406/AT-406) of Multiple Inhibitor of Apoptosis Proteins (IAPs) in Clinical Development for Cancer Treatment
  作者：Qian Cai、Haiying Sun、Yuefeng Peng、Jianfeng Lu、Zaneta Nikolovska-Coleska、Donna McEachern、Liu Liu、Su Qiu、Chao-Yie Yang、Rebecca Miller、Han Yi、Tao Zhang、Duxin Sun、Sanmao Kang、Ming Guo、Lance Leopold、Dajun Yang、Shaomeng Wang

  DOI：10.1021/jm101505d

  日期：2011.4.28

  We report the discovery and characterization of SM-406 (compound 2), a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). This compound binds to XIAP, cIAP1, and cIAP2 proteins with K(i) of 66.4, 1.9, and 5.1 nM, respectively. Compound 2 effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Compound 2 is currently in phase I clinical trials for the treatment of human cancer.