tert-butyl ((S)-1-(((3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-(2-((2-chlorobenzyl)amino)ethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate | 1366595-58-5

• 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 ((S)-1-(((3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-(2-((2-chlorobenzyl)amino)ethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate
• CAS: 1366595-58-5
• 化学式: C₄₂H₅₄ClN₅O₅
• 分子量: 744.374
• InChiKey: UFZSKOWZMUDJTE-INBIQSTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.63
• 重原子数：
  53.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  120.08
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((S)-1-(((3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-(2-((2-chlorobenzyl)amino)ethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate 在 盐酸 、 甲醇 作用下， 以89%的产率得到(3S,6S,7R,9aS)-N-benzhydryl-7-[2-[(2-chlorophenyl)methylamino]ethyl]-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxamide
  参考文献：
  名称：

  Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents

  摘要：

  A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.098
• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-(cyanomethyl)-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-6-yl]amino]-1-oxobutan-2-yl]-N-methylcarbamate 在 sodium tetrahydroborate 、 氢气 、 N,N-二异丙基乙胺 、 柠檬酸 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 20.0~60.0 ℃ 、6.0 MPa 条件下， 反应 25.17h， 生成 tert-butyl ((S)-1-(((3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-7-(2-((2-chlorobenzyl)amino)ethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate
  参考文献：
  名称：

  Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents

  摘要：

  A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.098