6-Tert-butyl 4-ethyl 2-(methylthio)-7,8-dihydropyrido[4,3-D]pyrimidine-4,6(5H)-dicarboxylate | 1279816-50-0

• 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: 6-Tert-butyl 4-ethyl 2-(methylthio)-7,8-dihydropyrido[4,3-D]pyrimidine-4,6(5H)-dicarboxylate
• 英文别名: 6-O-tert-butyl 4-O-ethyl 2-methylsulfanyl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-4,6-dicarboxylate
• CAS: 1279816-50-0
• 化学式: C₁₆H₂₃N₃O₄S
• 分子量: 353.442
• InChiKey: PFIFWKMQZMQGAF-UHFFFAOYSA-N

物化性质

• 沸点：
  511.2±50.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-Tert-butyl 4-ethyl 2-(methylthio)-7,8-dihydropyrido[4,3-D]pyrimidine-4,6(5H)-dicarboxylate 在 盐酸 、 三乙基硅烷 、 bis(tri-t-butylphosphine)palladium(0) 、 N-甲基二环己基胺 、 palladium 10% on activated carbon 、 氨 、 sodium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 49.0h， 生成 2-(ethylamino)-6-(3-(4-(trifluoromethoxy)phenyl)propanoyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-4-carboxamide
  参考文献：
  名称：

  Identification of Tetrahydropyrido[4,3-d]pyrimidine Amides as a New Class of Orally Bioavailable TGR5 Agonists

  摘要：

  Takeda G-protein-coupled receptor 5 (TGR5) represents an exciting biological target for the potential treatment of diabetes and metabolic syndrome. A new class of high-throughput screening (HTS)-derived tetrahydropyrido[4,3-d]pyrimidine amide TGR5 agonists is disclosed. We describe our effort to identify an orally available agonist suitable for assessment of systemic TGR5 agonism. This effort resulted in identification of 16, which had acceptable potency and pharmacokinetic properties to allow for in vivo assessment in dog. A key aspect of this work was the calibration of human and dog in vitro assay systems that could be linked with data from a human ex vivo peripheral blood monocyte assay that expresses receptor at endogenous levels. Potency from the human in vitro assay was also found to correlate with data from an ex vivo human whole blood assay. This calibration exercise provided confidence that 16 could be used to drive plasma exposures sufficient to test the effects of systemic activation of TGR5.

  DOI：

  10.1021/ml300277t
• 作为产物：
  描述：

  4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester 在 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 6-Tert-butyl 4-ethyl 2-(methylthio)-7,8-dihydropyrido[4,3-D]pyrimidine-4,6(5H)-dicarboxylate
  参考文献：
  名称：

  Identification of Tetrahydropyrido[4,3-d]pyrimidine Amides as a New Class of Orally Bioavailable TGR5 Agonists

  摘要：

  Takeda G-protein-coupled receptor 5 (TGR5) represents an exciting biological target for the potential treatment of diabetes and metabolic syndrome. A new class of high-throughput screening (HTS)-derived tetrahydropyrido[4,3-d]pyrimidine amide TGR5 agonists is disclosed. We describe our effort to identify an orally available agonist suitable for assessment of systemic TGR5 agonism. This effort resulted in identification of 16, which had acceptable potency and pharmacokinetic properties to allow for in vivo assessment in dog. A key aspect of this work was the calibration of human and dog in vitro assay systems that could be linked with data from a human ex vivo peripheral blood monocyte assay that expresses receptor at endogenous levels. Potency from the human in vitro assay was also found to correlate with data from an ex vivo human whole blood assay. This calibration exercise provided confidence that 16 could be used to drive plasma exposures sufficient to test the effects of systemic activation of TGR5.

  DOI：

  10.1021/ml300277t