(3S,6S,7R,9aS)-N-benzhydryl-7-[2-[(3,5-dichlorophenyl)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 | 1366595-81-4

• 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: (3S,6S,7R,9aS)-N-benzhydryl-7-[2-[(3,5-dichlorophenyl)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
• CAS: 1366595-81-4
• 化学式: C₃₇H₄₅Cl₂N₅O₃
• 分子量: 678.702
• InChiKey: VMZLJSJMQIJQNE-ANAOGEIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  47
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3aS,5R,7aS,9aS)-3-benzyl-4-oxo-decahydro-2-oxa-3,4a-diazacyclopenta[f]azulene-5-carboxylic acid tert-butyl ester 在 盐酸 、 甲醇 、 三乙基硅烷 、 sodium tetrahydroborate 、 甲烷磺酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 柠檬酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 85.0 ℃ 、6.0 MPa 条件下， 反应 67.51h， 生成 (3S,6S,7R,9aS)-N-benzhydryl-7-[2-[(3,5-dichlorophenyl)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

文献信息

• Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents
  作者：Aldo Bianchi、Marcello Ugazzi、Luca Ferrante、Daniele Lecis、Cinzia Scavullo、Eloise Mastrangelo、Pierfausto Seneci

  DOI：10.1016/j.bmcl.2012.01.098

  日期：2012.3

  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.