ethyl 1-(cyclopropylmethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate | 1151740-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 1-(cyclopropylmethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate
• 英文别名: Ethyl 1-(cyclopropylmethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,5-naphthyridine-3-carboxylate
• CAS: 1151740-39-4
• 化学式: C₂₂H₂₁FN₂O₄
• 分子量: 396.418
• InChiKey: MMIADXBECWJAKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  C₂₄H₂₇FN₂O₅ 在 乙醇 、 sodium ethanolate 作用下， 以99%的产率得到ethyl 1-(cyclopropylmethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate
  参考文献：
  名称：

  Synthesis and Antiviral Activity of 7-Benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV Integrase Inhibitors

  摘要：

  The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naphthyridinone ring system. Low nanomolar IC50 values were achieved in an HIV-integrase strand transfer assay with both carboxylic ester and carboxamide groups at C-3. More importantly, several carboxamide congeners showed potent antiviral activity in cellular assays. A 7-benzyl substituent was found to be critical for potent enzyme inhibition, and an N-(2-methoxyethyl)-carboxamide moiety at C-3 significantly reduced plasma protein binding effects in vitro. Pharmacokinetic data in rats for one carboxamide analogue demonstrated oral bioavailability and reasonable in vivo clearance.

  DOI：

  10.1021/jm801404b