2-(3,3-difluoroazetidin-1-yl)-5-nitropyridine | 939376-82-6

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-(3,3-difluoroazetidin-1-yl)-5-nitropyridine
• 英文别名: 5-nitro-2-(3,3-difluoroazetidin-1-yl)pyridine
• CAS: 939376-82-6
• 化学式: C₈H₇F₂N₃O₂
• 分子量: 215.159
• InChiKey: YSTMHIXCNQODKK-UHFFFAOYSA-N

物化性质

• 沸点：
  359.9±42.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  62
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3,3-difluoroazetidin-1-yl)-5-nitropyridine 在 5% Pd(II)/C(eggshell) 、 氢气 、 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-phenyl-5-trifluoromethyloxazole-4-carboxylic acid [6-(3,3-difluoroazetidin-1-yl)pyridin-3-yl]amide
  参考文献：
  名称：

  Discovery of Orally Active Carboxylic Acid Derivatives of 2-Phenyl-5-trifluoromethyloxazole-4-carboxamide as Potent Diacylglycerol Acyltransferase-1 Inhibitors for the Potential Treatment of Obesity and Diabetes

  摘要：

  Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxarnides. In particular, compound 29 (DGAT-1 enzyme assay, IC(50) = 57 nM; CHO-K1 cell triglyceride formation assay, EC(50) = 0.5 mu M) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, PO, qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT).

  DOI：

  10.1021/jm101580m
• 作为产物：
  描述：

  2-氯-5-硝基吡啶 、 3,3-二氟三甲叉亚胺 盐酸盐 在 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以to give 5-nitro-2-(3,3-difluoroazetidin-1-yl)pyridine的产率得到2-(3,3-difluoroazetidin-1-yl)-5-nitropyridine
  参考文献：
  名称：

  DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS

  摘要：

  本文提供了以下式(I)的化合物及其药学上可接受的盐，其中取代基如规范中所述。这些化合物及含有它们的药物组成物，可用于治疗疾病，例如肥胖症、2型糖尿病和代谢综合征。

  公开号：

  US20100190979A1

文献信息

• Diacylglycerol acyltransferase inhibitors
  申请人：Bolin Robert David

  公开号：US20070123504A1

  公开（公告）日：2007-05-31

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

  本文提供了式(I)的化合物，以及其药学上可接受的盐，其中取代基如规范中所披露的那样。这些化合物及含有它们的药物组合物对于治疗诸如肥胖、2型糖尿病和代谢综合征等疾病是有用的。
• N-(amino-heteroaryl)-1H-pyrrolopyridine-2-carboxamides derivatives preparation thereof and their use in therapy
  申请人：DUBOIS Laurent

  公开号：US20100041634A1

  公开（公告）日：2010-02-18

  The invention relates to compounds of the general formula (I): Wherein X, Y, Z, Z 1 , Z 2 , Z 3 , Z 4 and n are as defined herein. The invention also relates to a method for making the same and to the use thereof in therapy.

  该发明涉及一般式(I)的化合物：其中X、Y、Z、Z1、Z2、Z3、Z4和n如本文所定义。该发明还涉及制备该化合物的方法以及在治疗中的应用。
• DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS
  申请人：Bolin David Robert

  公开号：US20100190979A1

  公开（公告）日：2010-07-29

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

  本文提供了以下式(I)的化合物及其药学上可接受的盐，其中取代基如规范中所述。这些化合物及含有它们的药物组成物，可用于治疗疾病，例如肥胖症、2型糖尿病和代谢综合征。
• Diacylglycerol Acyltransferase Inhibitors
  申请人：Bolin David Robert

  公开号：US20100168419A1

  公开（公告）日：2010-07-01

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

  本文所提供的化合物具有公式（I）的结构，以及其药学上可接受的盐，其中取代基与规范中所披露的相同。这些化合物以及含有它们的制药组合物，可用于治疗疾病，例如肥胖症、2型糖尿病和代谢综合征。
• N-(amino-heteroaryI)-1H-pyrrolopyridine-2-carboxamides derivatives preparation thereof and their use in therapy
  申请人：Dubois Laurent

  公开号：US08716272B2

  公开（公告）日：2014-05-06

  The invention relates to compounds of the general formula (I): Wherein X, Y, Z, Z1, Z2, Z3, Z4 and n are as defined herein. The invention also relates to a method for making the same and to the use thereof in therapy.

  本发明涉及一般式（I）的化合物：其中X，Y，Z，Z1，Z2，Z3，Z4和n如本文所定义。本发明还涉及制备该化合物的方法以及在治疗中的使用。