endo-tert-butyl 3-(6-(2-fluoro-4-(methylsulfonyl)phenylamino)-5-nitropyrimidin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate | 1424328-56-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: endo-tert-butyl 3-(6-(2-fluoro-4-(methylsulfonyl)phenylamino)-5-nitropyrimidin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate
• CAS: 1424328-56-2
• 化学式: C₂₃H₂₈FN₅O₇S
• 分子量: 537.569
• InChiKey: CUVZAJHHFOUFRH-FICVDOATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  153.86
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  endo-tert-butyl 3-(6-(2-fluoro-4-(methylsulfonyl)phenylamino)-5-nitropyrimidin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate 在 盐酸 、 三乙胺 作用下， 以 乙醇 为溶剂， 生成 endo-ethyl 3-(6-(2-fluoro-4-(methylsulfonyl)phenylamino)-5-nitropyrimidin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  带有内氮杂双环醇/胺作为强效GPR119激动剂的新型5-硝基嘧啶衍生物

  摘要：

  合成了一系列基于带有内氮杂双环取代基的5-硝基嘧啶骨架的GPR119激动剂，并评估了它们的GPR119激动活性。大多数化合物的EC 50值比油酰乙醇酰胺（OEA）强得多。其中，来自内-氮杂双环醇的衍生物比具有内-氮杂双环胺的化合物显示出更强的GPR119激动活性。特别优化的化合物（6，7，8，12，17）显示出具有有效的生物活性和被确定为完全激动剂。氨基甲酸异丙酯化合物8观察到由内氮杂双环醇合成的EC 50值最佳（0.6 nM）。通常，在5-硝基嘧啶支架的C4位上的芳基被2-氟取代导致生物活性的增加。

  DOI：

  10.1016/j.bmc.2016.10.030
• 作为产物：
  描述：

  [2-氟-4-(甲基硫代)苯基]胺 在 间氯过氧苯甲酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 endo-tert-butyl 3-(6-(2-fluoro-4-(methylsulfonyl)phenylamino)-5-nitropyrimidin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists

  摘要：

  5-Nitropyrimidine analogs substituted with conformationally restricted azabicyclic amines and alcohols were prepared and evaluated their agonistic activity against human GPR119. The analogs bearing endo-azabicyclic amines and alcohols (7, 8, 11, and 12) exhibited full agonistic activities while the analogs with exo-azabicyclic amines and alcohols were proved as partial agonists (9, 10, 13, and 14) regardless of their EC50 values. 5-Nitropyrimidine analogs with (2-fluoro-4-methylsulfonyl)phenylamino group (8, 10, 12, 14) showed more potent GPR119 activation activities than the analogs without fluorine in all cases (7, 9, 11, 13). (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.011

文献信息

• Novel 5-nitropyrimidine derivatives bearing endo-azabicyclic alcohols/amines as potent GPR119 agonists
  作者：Yuanying Fang、Zunhua Yang、Shankariah Gundeti、Jongkook Lee、Haeil Park

  DOI：10.1016/j.bmc.2016.10.030

  日期：2017.1

  activities. Most compounds exhibited much stronger EC50 values than that of oleoylethanolamide (OEA). Among them, derivatives from endo-azabicyclic alcohols displayed more potent GPR119 agonistic activities than compounds with endo-azabicyclic amines. Especially the optimized compounds (6, 7, 8, 12, 17) were shown to have potent biological activities and were identified as full agonists. Isopropyl carbamate

  合成了一系列基于带有内氮杂双环取代基的5-硝基嘧啶骨架的GPR119激动剂，并评估了它们的GPR119激动活性。大多数化合物的EC 50值比油酰乙醇酰胺（OEA）强得多。其中，来自内-氮杂双环醇的衍生物比具有内-氮杂双环胺的化合物显示出更强的GPR119激动活性。特别优化的化合物（6，7，8，12，17）显示出具有有效的生物活性和被确定为完全激动剂。氨基甲酸异丙酯化合物8观察到由内氮杂双环醇合成的EC 50值最佳（0.6 nM）。通常，在5-硝基嘧啶支架的C4位上的芳基被2-氟取代导致生物活性的增加。
• Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists
  作者：Zunhua Yang、Yuanying Fang、Tuan-Anh N. Pham、Jongkook Lee、Haeil Park

  DOI：10.1016/j.bmcl.2012.12.011

  日期：2013.3

  5-Nitropyrimidine analogs substituted with conformationally restricted azabicyclic amines and alcohols were prepared and evaluated their agonistic activity against human GPR119. The analogs bearing endo-azabicyclic amines and alcohols (7, 8, 11, and 12) exhibited full agonistic activities while the analogs with exo-azabicyclic amines and alcohols were proved as partial agonists (9, 10, 13, and 14) regardless of their EC50 values. 5-Nitropyrimidine analogs with (2-fluoro-4-methylsulfonyl)phenylamino group (8, 10, 12, 14) showed more potent GPR119 activation activities than the analogs without fluorine in all cases (7, 9, 11, 13). (c) 2012 Elsevier Ltd. All rights reserved.