6-(methyl(phenyl)amino)[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol | 885260-70-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-(methyl(phenyl)amino)[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol
• 英文别名: 6-(N-methyl-N-phenylamino)-[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol；5-(N-methylanilino)-7H-[1,2,5]oxadiazolo[3,4-b]pyrazin-6-one
• CAS: 885260-70-8
• 化学式: C₁₁H₉N₅O₂
• 分子量: 243.225
• InChiKey: ZJYYQINUEQQSKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5,6-二氯-[1,2,5]恶二唑并[3,4-B]吡嗪 、 N-甲基苯胺 在 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以93%的产率得到6-(methyl(phenyl)amino)[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol
  参考文献：
  名称：

  6-氨基[1,2,5]恶二唑并[3,4-b]吡嗪-5-醇衍生物作为非酒精性脂肪性肝炎 STAM 小鼠模型中有效的线粒体解偶联剂。

  摘要：

  小分子线粒体解偶联剂最近因其在治疗非酒精性脂肪性肝炎（NASH）方面的潜力而引起了人们的极大兴趣。在这项研究中，我们报告了 6-氨基[1,2,5]恶二唑并[3,4- b ]pyrazin-5-ol 核心的结构-活性关系分析，该核心利用羟基部分作为跨膜的质子转运蛋白。线粒体内膜。我们证明，这种新型支架可以耐受多种取代基，该支架可以通过耗氧率的变化作为读数来增加体外细胞代谢率。特别是，化合物SHS4121705 ( 12i ) 在 L6 成肌细胞中表现出 4.3 μM 的 EC 50 ，并且在小鼠中表现出优异的口服生物利用度和肝脏暴露。在 NASH 的 STAM 小鼠模型中，给予 25 mg kg –1天–1的12i降低了肝脏甘油三酯水平，并改善了肝脏标志物，如丙氨酸氨基转移酶、NAFLD 活动评分和纤维化。重要的是，没有观察到体温或食物摄入量的变化。作为 NASH 的潜在治疗方法，线粒体解偶联剂显示出未来发展的前景。

  DOI：

  10.1021/acs.jmedchem.0c00542

文献信息

• FURAZANO `3, 4-B ! PYRAZYNES AND THEIR USE AS ANTI-TUMOR AGENTS
  申请人：Compass Pharmaceuticals LLC

  公开号：EP1799689A1

  公开（公告）日：2007-06-27
• Furazano '3, 4-B! Pyrazines and Their Use as Anti-Tumor Agents
  申请人：Baures Paul W.

  公开号：US20090131445A1

  公开（公告）日：2009-05-21

  The present invention provides novel compounds of the formula (I) and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
• OXADIAZOLOPYRAZINES AND OXADIAZOLOPYRIDINES USEFUL AS MITOCHONDRIAL UNCOUPLERS
  申请人：Virginia Tech Intellectual Properties, Inc.

  公开号：US20210253594A1

  公开（公告）日：2021-08-19

  The disclosure provide compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R 1 , R 2 , R 3 , X 1 , X 2 , and Z are defined herein. Certain compounds of Formula I act as selective mitochondrial protonophore uncouplers that do not affect the plasma membrane potential. Compounds and salts of Formula I are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as cancer, 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). Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, compounds of Formula I are useful for increasing lifespan. Compounds and salts of Formula I are also useful for regulating glucose homeostasis or insulin action in a patient.
• [EN] FURAZANO `3, 4-B ! PYRAZYNES AND THEIR USE AS ANTI-TUMOR AGENTS<br/>[FR] FURAZANO-3,4-BIPYRAZINES ET LEUR EMPLOI EN TANT QU'AGENTS ANTITUMORAUX
  申请人：COMPASS PHARMACEUTICALS LLC

  公开号：WO2006044402A1

  公开（公告）日：2006-04-27

  [EN] The present invention provides novel compounds of the formula (I) and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
  [FR] La présente invention décrit de nouveaux composés de formule (I) et des préparations pharmaceutiques incluant lesdits composés, ainsi que des méthodes permettant d'employer lesdits composés et lesdites préparations pharmaceutiques dans le traitement de tumeurs. Lesdits composés peuvent être employés afin de traiter des tumeurs spécifiques, par exemple les sarcomes, les mélanomes, les neuroblastomes, les carcinomes (incluant sans y être limités les carcinomes du poumon, des cellules rénales, ovariens, du foie, de la vessie, et pancréatiques) et les mésothéliomes.
• [EN] OXADIAZOLOPYRAZINES AND OXADIAZOLOPYRIDINES USEFUL AS MITOCHONDRIAL UNCOUPLERS<br/>[FR] OXADIAZOLOPYRAZINES ET OXADIAZOLOPYRIDINES UTILISÉES COMME DÉCOUPLANTS MITOCHONDRIAUX
  申请人：VIRGINIA TECH INTELLECTUAL PROPERTIES INC

  公开号：WO2019204813A1

  公开（公告）日：2019-10-24

  The disclosure provide compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R1, R2, R3, X1, X2, and Z are defined herein. Certain compounds of Formula I act as selective mitochondrial protonophore uncouplers that do not affect the plasma membrane potential. Compounds and salts of Formula I are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as cancer, 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). Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, compounds of Formula I are useful for increasing lifespan. Compounds and salts of Formula I are also useful for regulating glucose homeostasis or insulin action in a patient.