6-氯-N-(4-甲基磺酰基苯基)-5-硝基嘧啶-4-胺 | 733751-06-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 6-氯-N-(4-甲基磺酰基苯基)-5-硝基嘧啶-4-胺
• 英文名称: 6-chloro-N-(4-(methylsulfonyl)phenyl)-5-nitropyrimidin-4-amine
• 英文别名: (6-chloro-5-nitro-pyrimidin-4-yl)-(4-methanesulfonyl-phenyl)-amine；6-chloro-N-(4-methylsulfonylphenyl)-5-nitropyrimidin-4-amine
• CAS: 733751-06-9
• 化学式: C₁₁H₉ClN₄O₄S
• 分子量: 328.736
• InChiKey: ZXRRXNGREHGPMS-UHFFFAOYSA-N

物化性质

• 沸点：
  551.2±50.0 °C(Predicted)
• 密度：
  1.584±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 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：
  7

反应信息

• 作为反应物：
  描述：

  6-氯-N-(4-甲基磺酰基苯基)-5-硝基嘧啶-4-胺 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以60%的产率得到3-[6-(4-methanesulfonyl-phenylamino)-5-nitro-pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] TRISUBSTITUTED ARYL AND HETEROARYL DERIVATIVES AS MODULATORS OF METABOLISM AND THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO
  [FR] DERIVES ARYLES ET HETEROARYLES TRISUBSTITUES UTILISES EN TANT QUE MODULATEURS DU METABOLISME ET PROPHYLAXIE ET TRAITEMENT DE TROUBLES AFFERENTS

  摘要：

  本发明涉及公式（I）的某些三取代芳基和杂环芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢紊乱及其并发症，如糖尿病和肥胖方面是有用的。

  公开号：

  WO2005007647A1
• 作为产物：
  描述：

  4-氨基茴香硫醚 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-氯-N-(4-甲基磺酰基苯基)-5-硝基嘧啶-4-胺
  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

• 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％）。
• [EN] 1,2,3-TRISUBSTITUTED ARYL AND HETEROARYL DERIVATIVES AS MODULATORS OF METABOLISM AND THE PRPPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO SUCH AS DIABETES AND HYPERGLYCEMIA<br/>[FR] DERIVES ARYLES ET HETEROARYLES TRI-SUBSTITUES EN POSITION 1,2,3 EN TANT QUE MODULATEURS DE METABOLISME ET PROPHYLAXIE ET TRAITEMENT DE TROUBLES LIES AU METABOLISME
  申请人：ARENA PHARM INC

  公开号：WO2004065380A1

  公开（公告）日：2004-08-05

  The present invention relates to certain 1,2,3-trisubstituted aryl and heteroaryl derivatives of Fomula (Ia) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及某些Fomula（Ia）的1,2,3-三取代芳基和杂芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢紊乱及其并发症，如糖尿病和肥胖方面是有用的。
• 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。
• 이중환 구조를 갖는 신규한 ＧＰＣＲ 효능제
  申请人：KNU-Industry Cooperation Foundation 강원대학교산학협력단(220040088571) BRN ▼221-82-10213

  公开号：KR101705390B1

  公开（公告）日：2017-02-09

  본 발명은 이중환 구조를 갖는 신규한 GPCR 효능제에 관한 것으로서, 보다 자세하게 본 발명은 이중환 구조를 갖는 GPR119(Glucose-protein coupled receptor 119)의 활성을 촉진시키는 작용을 갖는 신규 화합물, 이의 약학적으로 허용 가능한 염 및 상기 화합물을 유효성분으로 포함하는 비만, 비만 관련 질환, 당뇨병, 당뇨합병증, 대사장애 및 심혈관 질환으로 이루어진 군 중에서 선택되는 질환의 예방 및 치료용 조성물에 관한 것이다.

  本发明涉及一种具有双环结构的新GPCR药物，更具体地，本发明涉及一种具有促进具有双环结构的GPR119（葡萄糖-蛋白质耦合受体119）活性的作用的新化合物，以及其药学上可接受的盐和包含其有效成分的用于预防和治疗包括肥胖症，肥胖相关疾病，糖尿病，糖尿病并发症，代谢障碍和心血管疾病在内的疾病中选择的组合物。
• Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto
  申请人：Jones M. Robert

  公开号：US20060142262A1

  公开（公告）日：2006-06-29

  The present invention relates to certain fused aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些融合芳基和杂芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢性疾病及其并发症方面非常有用，如糖尿病和肥胖症。