tert-butyl 4-(methylthio)-5-oxo-2-phenyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate | 1345014-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: tert-butyl 4-(methylthio)-5-oxo-2-phenyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate
• 英文别名: Tert-butyl 4-methylsulfanyl-5-oxo-2-phenyl-7,8-dihydropyrido[4,3-d]pyrimidine-6-carboxylate
• CAS: 1345014-04-1
• 化学式: C₁₉H₂₁N₃O₃S
• 分子量: 371.46
• InChiKey: DUQKRTFHSPVJKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  97.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(methylthio)-5-oxo-2-phenyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 在 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 11.5h， 生成 4-[(3-methoxyphenyl)amino]-2-phenyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one
  参考文献：
  名称：

  4-Amino-7,8-dihydro-1,6-naphthyridin-5(6H)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure–Activity Relationships

  摘要：

  Rational design of a novel template of naphthyridinones rapidly led to PDE4 inhibitors with subnanomolar enzymatic potencies. X-ray crystallography confirmed the binding mode of this novel template. We achieved compounds with double-digit picomolar enzymatic potencies through further structure-based design by targeting both the PDE4 enzyme metal binding pocket and occupying the solvent-filled pocket. A strategy for lung retention and long duration of action based on low aqueous solubility was followed. In vivo efficacies were measured in a rat lung neutrophilia model by suspension microspray and dry powder administration. Suspension microspray of potent compounds showed in vivo efficacy with a clear dose-response. Despite sustained lung levels, dry powder administration performed much less well and without proper dose-response, highlighting clear differences between the two formulations. This indicates a deficiency in the low aqueous solubility strategy for long duration lung efficacy.

  DOI：

  10.1021/acs.jmedchem.7b01751
• 作为产物：
  描述：

  tert-butyl 3-[bis(methylthio)methylene]-2,4-dioxopiperidine-1-carboxylate 、 苄脒盐酸盐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 48.08h， 生成 tert-butyl 4-(methylthio)-5-oxo-2-phenyl-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate
  参考文献：
  名称：

  New 7,8-dihydro-1,6-naphthyridin-5(6h)-one-derivatives as PDE4 inhibitors

  摘要：

  揭示了具有化学结构式（I）的新的7,8-二氢-1,6-萘啶-5(6H)-酮衍生物衍生物；以及它们的制备方法，包含它们的药物组合物以及它们作为磷酸二酯酶IV（PDE4）抑制剂在治疗中的用途。

  公开号：

  EP2380890A1