5-{(E)-1-(4-Methanesulfonyl-phenyl)-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-vinyl}-3-methyl-[1,2,4]oxadiazole | 871107-97-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 5-{(E)-1-(4-Methanesulfonyl-phenyl)-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-vinyl}-3-methyl-[1,2,4]oxadiazole
• CAS: 871107-97-0
• 化学式: C₂₄H₂₇BN₂O₅S
• 分子量: 466.366
• InChiKey: JHFXGVHXRIAJLB-RCCKNPSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  91.52
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  8-bromo-6-isopropyl-quinoline 、 5-{(E)-1-(4-Methanesulfonyl-phenyl)-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-vinyl}-3-methyl-[1,2,4]oxadiazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-isopropyl-8-(3-{(E)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-[4-(methylsulfonyl)phenyl]ethenyl}phenyl)quinoline
  参考文献：
  名称：

  Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

  摘要：

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.036
• 作为产物：
  描述：

  5-[(E)-2-(3-Bromo-phenyl)-1-(4-methanesulfonyl-phenyl)-vinyl]-3-methyl-[1,2,4]oxadiazole 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-{(E)-1-(4-Methanesulfonyl-phenyl)-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-vinyl}-3-methyl-[1,2,4]oxadiazole
  参考文献：
  名称：

  Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

  摘要：

  The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC50 < 1 nM) and also of LPS-induced TNF-alpha release in human whole blood (IC50 < 0.5 mu M). The same compounds are potent inhibitors of ovalbumin-induced bronchoconstriction in conscious guinea pigs (EC50 < 0.1 mg/kg ip) but require a dose of about 10 mg/kg po in the squirrel monkey to produce an emetic response. From this series of compounds, 23a (L-454,560) was identified as an optimized compound. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.036