6-chloro-N-(2-fluoro-4-(methylsulfonyl)phenyl)-5-nitropyrimidin-4-amine | 1310693-13-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-chloro-N-(2-fluoro-4-(methylsulfonyl)phenyl)-5-nitropyrimidin-4-amine
• 英文别名: 6-chloro-N-(2-fluoro-4-methylsulfonylphenyl)-5-nitropyrimidin-4-amine
• CAS: 1310693-13-0
• 化学式: C₁₁H₈ClFN₄O₄S
• 分子量: 346.726
• InChiKey: LELLCVAYSHFRTR-UHFFFAOYSA-N

物化性质

• 沸点：
  521.3±50.0 °C(Predicted)
• 密度：
  1.637±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-chloro-N-(2-fluoro-4-(methylsulfonyl)phenyl)-5-nitropyrimidin-4-amine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 6-chloro-9-(2-fluoro-4-(methylsulfonyl)phenyl)-7,9-dihydro-8H-purin-8-one
  参考文献：
  名称：

  在葡萄糖控制的啮齿动物模型中发现具有体内活性的孤儿G蛋白偶联受体GPR119的稠合双环激动剂

  摘要：

  我们在此概述了胰腺和GI表达的孤儿G蛋白偶联受体GPR119的新系列激动剂的设计，该激动剂是从原型激动剂AR231453开始的，在代谢领域中最近引起了人们的极大关注。首先通过并入吡唑并嘧啶核以创建新的结构系列，然后通过引入被氨基甲酸酯封端的哌啶醚基，改善了许多关键参数。长期使用该系列化合物中的一种3k进行的长期治疗首次显示，在数周的服药期间，Zucker糖尿病脂肪（ZDF）大鼠的血糖和糖化血红蛋白（HbA1c）水平可能显着降低。由于此处描述的这些数据和其他数据，因此3k （APD668，JNJ-28630368）是第一种具有这种作用机制的化合物，已被开发用于临床治疗糖尿病。

  DOI：

  10.1016/j.bmcl.2011.03.007
• 作为产物：
  描述：

  [2-氟-4-(甲基硫代)苯基]胺 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-chloro-N-(2-fluoro-4-(methylsulfonyl)phenyl)-5-nitropyrimidin-4-amine
  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 pyrimidine derivatives with diverse azabicyclic ether/amine as novel GPR119 agonist
  作者：Zunhua Yang、Yuanying Fang、Haeil Park

  DOI：10.1016/j.bmcl.2017.03.092

  日期：2017.6

  A class of novel pyrimidine derivatives bearing diverse conformationally restricted azabicyclic ether/amine were designed, synthesized and evaluated for their GPR119 agonist activities against type 2 diabetes. Most compounds exhibited superior hEC50 values to endogenous lipid oleoylethanolamide (OEA). Analogs with 2-fluoro substitution in the aryl ring showed more potent GPR119 activation than those

  设计，合成并评估了一类新型的嘧啶衍生物，它们带有各种构象受限的氮杂双环醚/胺，并针对2型糖尿病评估了其GPR119激动剂活性。大多数化合物显示出比内源性脂质油酰乙醇酰胺（OEA）更高的hEC50值。在芳基环中具有2-氟取代基的类似物显示出比没有氟的类似物更有效的GPR119活化。尤其是，从内氮杂双环醇合成的化合物27m被认为具有最佳的EC50值（1.2nM）和作为完全激动剂的相当好的激动活性（最大112.2％）。
• Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control
  作者：Graeme Semple、Albert Ren、Beatriz Fioravanti、Guillherme Pereira、Imelda Calderon、Karoline Choi、Yifeng Xiong、Young-Jun Shin、Tawfik Gharbaoui、Carleton R. Sage、Michael Morgan、Charles Xing、Zhi-Liang Chu、James N. Leonard、Andrew J. Grottick、Hussein Al-Shamma、Yin Liang、Keith T. Demarest、Robert M. Jones

  DOI：10.1016/j.bmcl.2011.03.007

  日期：2011.5

  We herein outline the design of a new series of agonists of the pancreatic and GI-expressed orphan G-protein coupled receptor GPR119, a target that has been of significant recent interest in the field of metabolism, starting from our prototypical agonist AR231453. A number of key parameters were improved first by incorporation of a pyrazolopyrimidine core to create a new structural series and secondly

  我们在此概述了胰腺和GI表达的孤儿G蛋白偶联受体GPR119的新系列激动剂的设计，该激动剂是从原型激动剂AR231453开始的，在代谢领域中最近引起了人们的极大关注。首先通过并入吡唑并嘧啶核以创建新的结构系列，然后通过引入被氨基甲酸酯封端的哌啶醚基，改善了许多关键参数。长期使用该系列化合物中的一种3k进行的长期治疗首次显示，在数周的服药期间，Zucker糖尿病脂肪（ZDF）大鼠的血糖和糖化血红蛋白（HbA1c）水平可能显着降低。由于此处描述的这些数据和其他数据，因此3k （APD668，JNJ-28630368）是第一种具有这种作用机制的化合物，已被开发用于临床治疗糖尿病。
• 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.