N5,N6-bis(2,4-difluorophenyl)[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine | 309742-72-1

• 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: N5,N6-bis(2,4-difluorophenyl)[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine
• 英文别名: Furazano[3,4-b]pyrazine-5,6-diamine, N,N'-di(2,4-difluorophenyl)-；5-N,6-N-bis(2,4-difluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine
• CAS: 309742-72-1
• 化学式: C₁₆H₈F₄N₆O
• 分子量: 376.273
• InChiKey: HZEKCJKVAIEXDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88.8
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,4-二氟苯胺 、 5,6-二氯-[1,2,5]恶二唑并[3,4-B]吡嗪 在 N,N-二乙基苯胺 作用下， 以 乙腈 为溶剂， 生成 N5,N6-bis(2,4-difluorophenyl)[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine
  参考文献：
  名称：

  呋喃并[3,4- b ]吡嗪作为线粒体解偶联剂的构效关系

  摘要：

  化学线粒体解偶联剂是亲脂性弱酸，它们通过独立于ATP合酶的途径将质子转运到线粒体基质中，从而使养分氧化与ATP产生脱钩。这些解耦剂具有治疗肥胖，帕金森氏病和衰老等疾病的潜力。我们之前已经确定了一种新型的线粒体质子体，称为BAM15，与羰基氰化物对-三氟甲氧基苯基hydr （FCCP）相比，该剂能在广泛的剂量范围内刺激线粒体呼吸。在此，我们报告了我们对BAM15的构效关系的研究。我们的研究证明了呋喃山，吡嗪和苯胺环以及p K的重要性a维持其有效的质子体活性。

  DOI：

  10.1016/j.bmcl.2015.06.040

文献信息

• [EN] COMPOSITIONS AND METHODS FOR PREPARING AND USING MITOCHONDRIAL UNCOUPLERS<br/>[FR] COMPOSITIONS ET MÉTHODES DE PRÉPARATION ET D'UTILISATION DE DÉCOUPLEURS MITOCHONDRIAUX
  申请人：UNIV VIRGINIA PATENT FOUNDATION

  公开号：WO2018217757A1

  公开（公告）日：2018-11-29

  This disclosure provides compounds of Formula I, II, and III and pharmaceutically acceptable salts thereof for use as mitochondrial uncouplers, where the variables, e.g. R1-R9, (I) (II) (III) X1, X2, and Y1 are defined in the specification. The disclosure also provides pharmaceutical compositions comprising a compound or pharmaceutically acceptable salt of Formula I, II, or III, alone or in combination with another active compound. Compounds and compositions of Formula I, II, and III are useful for treating or preventing certain conditions responsive to mitochondrial uncoupling such as obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Compounds of Formula I, II, and III are also useful for regulating glucose homeostatis and insulin action.

  本公开提供了化合物I、II和III及其药学上可接受的盐，用作线粒体解偶联剂，其中变量，例如R1-R9，（I）（II）（III）X1、X2和Y1在规范中定义。本公开还提供了包含化合物或化学上可接受的盐的药物组合物，单独或与另一种活性化合物结合使用。化合物和组合物I、II和III的公式对于治疗或预防对线粒体解偶联有响应的某些疾病条件是有用的，例如肥胖症、2型糖尿病、脂肪肝病、胰岛素抵抗、帕金森病、缺血再灌注损伤、心力衰竭、非酒精性脂肪肝病（NALFD）和非酒精性脂肪性肝炎（NASH）。化合物I、II和III的公式也对调节葡萄糖稳态和胰岛素作用有用。
• Compositions and methods for regulating glucose homeostasis and insulin action
  申请人：University of Virginia Patent Foundation

  公开号：US10479800B2

  公开（公告）日：2019-11-19

  The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl)6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

  本发明包括将化合物用于治疗和预防糖尿病和缺血再灌注损伤等疾病、病症和失调的新方法。本发明的化合物，包括但不限于线粒体解偶联剂 BAM15（(2-氟苯基)6-[(2-氟苯基)氨基](1,2,5-恶二唑并[3,4-e]吡嗪-5-基)}胺），可以改善葡萄糖耐量，增加细胞耗氧量，治疗或预防肾脏缺血再灌注损伤逆转胰岛素抵抗，逆转或治疗高胰岛素血症，逆转或治疗高脂血症。本发明进一步提供了新型化合物以及鉴定与 BAM15 具有相同或相似性质的化合物的方法。
• Compositions and methods of regulating glucose homeostasis and insulin action
  申请人：UNIVERSITY OF VIRGINIA

  公开号：US10683306B2

  公开（公告）日：2020-06-16

  The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl)6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

  本发明包括将化合物用于治疗和预防糖尿病和缺血再灌注损伤等疾病、病症和失调的新方法。本发明的化合物，包括但不限于线粒体解偶联剂 BAM15（(2-氟苯基)6-[(2-氟苯基)氨基](1,2,5-恶二唑并[3,4-e]吡嗪-5-基)}胺），可以改善葡萄糖耐量，增加细胞耗氧量，治疗或预防肾脏缺血再灌注损伤逆转胰岛素抵抗，逆转或治疗高胰岛素血症，逆转或治疗高脂血症。本发明进一步提供了新型化合物以及鉴定与 BAM15 具有相同或相似性质的化合物的方法。
• COMPOSITIONS AND METHODS FOR PREPARING AND USING MITOCHONDRIAL UNCOUPLERS
  申请人：University Of Virginia Patent Foundation

  公开号：EP3630115A1

  公开（公告）日：2020-04-08
• COMPOSITIONS AND METHODS FOR REGULATING GLUCOSE HOMEOSTASIS AND INSULIN ACTION
  申请人：University of Virginia Patent Foundation

  公开号：US20150322081A1

  公开（公告）日：2015-11-12

  The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15((2-fluorophenyl)6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.