tert-butyl 4-(4-(5-(4-cyanophenyl) furan-2-carboxamido)phenyl)piperazine-1-carboxylate | 1355617-72-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-(4-(5-(4-cyanophenyl) furan-2-carboxamido)phenyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-(4-(5-(4-cyanophenyl)furan-2-carboxamido)phenyl)piperazine-1-carboxylate；tert-butyl 4-[4-[[5-(4-cyanophenyl)furan-2-carbonyl]amino]phenyl]piperazine-1-carboxylate
• CAS: 1355617-72-9
• 化学式: C₂₇H₂₈N₄O₄
• 分子量: 472.544
• InChiKey: TZYQQQBVRUYXDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.13
• 重原子数：
  35.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  98.81
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(5-(4-cyanophenyl) furan-2-carboxamido)phenyl)piperazine-1-carboxylate 在 叠氮基三甲基硅烷 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 生成
  参考文献：
  名称：

  Discovery of a novel series of potent MK2 non-ATP competitive inhibitors using 1,2-substituted azoles as cis-amide isosteres

  摘要：

  A unified strategy was conceived and implemented to deliver conformationally constrained anilides based on their preferred cis-amide conformers. The imidazole/triazole mimicing amide bonds were designed, building upon an earlier discovery of a novel series of tricyclic lactams MK2 kinase inhibitors. This approach enabled rapid, modular synthesis of structurally novel analogs. The efficient SAR development led to the discovery of low molecular weight and potent MK2 non-ATP competitive inhibitors with good ligand efficiency, which led to improved permeability and oral exposure in rats. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.024
• 作为产物：
  描述：

  5-(4-氰基苯基)-2-糠酸 、 1-Boc-4-(4-氨基苯基)哌嗪 在 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到tert-butyl 4-(4-(5-(4-cyanophenyl) furan-2-carboxamido)phenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  A three-step protocol for lead optimization: Quick identification of key conformational features and functional groups in the SAR studies of non-ATP competitive MK2 (MAPKAPK2) inhibitors

  摘要：

  A three-step protocol for SAR development was introduced and applied to the SAR studies of the MK2 inhibitor program. Following this protocol, key conformational features and functional groups for improving MK2 inhibitor activity were quickly identified. Through this effort, the initial gap observed between in vitro binding activity and cellular activity in the lead identification stage was very much reduced. Compound 28 was identified with single digit binding activity (IC50 = 8 nM) and good cellular activity (EC50 = 310 nM). This provides further evidence that non-ATP-competitive binding MK2 inhibitors are feasible by targeting the outside ATP pocket. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.074