(4S,4aS,7S)-N-((S)-1-(1-(benzylamino)-1-oxo-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-yl)-4-(5-guanidinopentanamido)-1-oxohexahydro-1H-pyrrolo[1,2-c][1,3]oxazine-7-carboxamide | 1350519-95-7

• 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: (4S,4aS,7S)-N-((S)-1-(1-(benzylamino)-1-oxo-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-yl)-4-(5-guanidinopentanamido)-1-oxohexahydro-1H-pyrrolo[1,2-c][1,3]oxazine-7-carboxamide
• 英文别名: (4S,4aS,7S)-N-[(2S)-1-[[1-(benzylamino)-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-4-[5-(diaminomethylideneamino)pentanoylamino]-1-oxo-3,4,4a,5,6,7-hexahydropyrrolo[1,2-c][1,3]oxazine-7-carboxamide
• CAS: 1350519-95-7
• 化学式: C₃₅H₄₈N₈O₆
• 分子量: 676.816
• InChiKey: LOFBOXJTIYRTGW-CSUIVHMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  210
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl (2S,5S)-1-benzyl-5-(2-ethoxycarbonylmethyl)pyrrolidine-2-carboxylate 在 盐酸 、 六甲基磷酰三胺 、 锂硼氢 、 20 % Pd(OH)2/C 、 2,4,6-三异丙基苯磺酰叠氮化物 、 氢气 、 双(三甲基硅烷基)氨基钾 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 82.58h， 生成 (4S,4aS,7S)-N-((S)-1-(1-(benzylamino)-1-oxo-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-yl)-4-(5-guanidinopentanamido)-1-oxohexahydro-1H-pyrrolo[1,2-c][1,3]oxazine-7-carboxamide
  参考文献：
  名称：

  Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate

  摘要：

  Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3 beta. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3 beta mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 = 3.1 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.079

文献信息

• Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate
  作者：Sujeewa Ranatunga、Juan R. Del Valle

  DOI：10.1016/j.bmcl.2011.09.079

  日期：2011.12

  Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3 beta. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3 beta mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 = 3.1 mu M). (C) 2011 Elsevier Ltd. All rights reserved.