6-(cyclopentyloxy)-7-methoxy-N,1-diphenyl-3,4-dihydroisoquinoline-3-carboxamide

• 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: 6-(cyclopentyloxy)-7-methoxy-N,1-diphenyl-3,4-dihydroisoquinoline-3-carboxamide
• 英文别名: 6-cyclopentyloxy-7-methoxy-N,1-diphenyl-3,4-dihydroisoquinoline-3-carboxamide
• 化学式: C₂₈H₂₈N₂O₃
• 分子量: 440.542
• InChiKey: NDHYRPVCUXDJEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-环戊氧-4-甲氧基苯甲醛 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 氢气 、 sodium acetate 、 乙酸酐 、 sodium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.5h， 生成 6-(cyclopentyloxy)-7-methoxy-N,1-diphenyl-3,4-dihydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  用1-苯基-3,4-二氢异喹啉骨架发现新型磷酸二酯酶抑制剂4：基于结构的药物设计和片段鉴定。

  摘要：

  Currently, it is in urgent need to develop novel selective PDE4 inhibitors with novel structural scaffolds to overcome the adverse effects and improve the efficacy. Novel 1-phenyl-3,4-dihydroisoquinoline amide derivatives were developed as potential PDE4 inhibitors based on the structure-based drug design and fragment identification strategy. A SARs analysis was performed in substituents attached in the C-3 side chain phenyl ring, indicating that the attachment of methoxy group or halogen atom substitution at the ortho-position of the phenyl ring was helpful to enhance both inhibitory activity toward PDE4B and selectivity. Compound 15 with excellent selectivity, exhibited the most potent inhibition in vitro and in vivo, which is a promising lead for development of a new class of selective PDE4 inhibitors.

  DOI：

  10.1016/j.bmcl.2019.126720

文献信息

• Discovery of novel inhibitors of phosphodiesterase 4 with 1-phenyl-3,4-dihydroisoquinoline scaffold: Structure-based drug design and fragment identification
  作者：Yixian Liao、Xiuhua Jia、Yongmei Tang、Sumei Li、Yipeng Zang、Lei Wang、Zi-Ning Cui、Gaopeng Song

  DOI：10.1016/j.bmcl.2019.126720

  日期：2019.11

  Currently, it is in urgent need to develop novel selective PDE4 inhibitors with novel structural scaffolds to overcome the adverse effects and improve the efficacy. Novel 1-phenyl-3,4-dihydroisoquinoline amide derivatives were developed as potential PDE4 inhibitors based on the structure-based drug design and fragment identification strategy. A SARs analysis was performed in substituents attached in the C-3 side chain phenyl ring, indicating that the attachment of methoxy group or halogen atom substitution at the ortho-position of the phenyl ring was helpful to enhance both inhibitory activity toward PDE4B and selectivity. Compound 15 with excellent selectivity, exhibited the most potent inhibition in vitro and in vivo, which is a promising lead for development of a new class of selective PDE4 inhibitors.