2,5-dibromo-3-(4-chlorophenyl)pyrazine | 960248-02-6

• 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: 2,5-dibromo-3-(4-chlorophenyl)pyrazine
• 英文别名: 2,5-Dibromo-3-(4-chloro-phenyl)-pyrazine
• CAS: 960248-02-6
• 化学式: C₁₀H₅Br₂ClN₂
• 分子量: 348.424
• InChiKey: INOAXJJTEWLQBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,5-dibromo-3-(4-chlorophenyl)pyrazine 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 一氧化碳 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 mineral oil 为溶剂， 20.0~110.0 ℃ 、7.0 MPa 条件下， 反应 21.75h， 生成 6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyrazinecarboxylic acid methyl ester
  参考文献：
  名称：

  6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

  摘要：

  We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.

  DOI：

  10.1021/jm4010708
• 作为产物：
  描述：

  5-bromo-3-(4-chlorophenyl)-2-pyrazinamine 在 三甲基溴硅烷 、 亚硝酸异戊酯 作用下， 以 二溴甲烷 为溶剂， 反应 1.5h， 生成 2,5-dibromo-3-(4-chlorophenyl)pyrazine
  参考文献：
  名称：

  3-Pyridinecarboxamide derivatives as HDL-cholesterol raising agents

  摘要：

  本发明涉及一种提高HDL胆固醇的方法，包括向需要的患者施用以下公式的化合物： 其中A、G、R1至R8和R17如描述中所定义。

  公开号：

  US20080085906A1

文献信息

• Pyrazinecarboxamide derivatives as CB1 antagonists
  申请人：Hebeisen Paul

  公开号：US20070293509A1

  公开（公告）日：2007-12-20

  The present invention relates to compounds of the formula I: wherein R 1 to R 8 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors, such as obesity.

  本发明涉及以下式I的化合物： 其中R1至R8如描述和索赔中定义，并且其药学上可接受的盐。这些化合物对于治疗和/或预防与调节CB1受体相关的疾病，如肥胖症，是有用的。
• 3-Pyridinecarboxamide Derivatives as HDL-Cholesterol Raising Agents
  申请人：Andjelkovic Mirjana

  公开号：US20100267745A1

  公开（公告）日：2010-10-21

  The present invention relates to a method of raising HDL cholesterol comprising administering to a patient in need thereof a compound of the formula wherein A, G, R 1 to R 8 and R 17 are as defined in the description.

  本发明涉及一种提高HDL胆固醇的方法，包括向需要的患者给予下式化合物： 其中A、G、R1至R8和R17如描述中所定义。
• 3-PYRIDINECARBOXAMIDE DERIVATIVES AS HDL-CHOLESTEROL RAISING AGENTS
  申请人：Andjelkovic Mirjana

  公开号：US20090143409A1

  公开（公告）日：2009-06-04

  The present invention relates to a method of raising HDL cholesterol comprising administering to a patient in need thereof a compound of the formula wherein A, G, R 1 to R 8 and R 17 are as defined in the description.

  本发明涉及一种提高HDL胆固醇的方法，包括向需要的患者给予以下式子中的化合物：其中A、G、R1到R8和R17如描述中所定义。
• 3-Pyridinecarboxamide and 2-pyrazinecarboxamide derivatives as HDL-cholesterol raising agents
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2450350A1

  公开（公告）日：2012-05-09

  The present invention relates to the use of compounds of the formula wherein A, G, R1 to R8 and R17 are as defined in the description, for the preparation of medicaments for the treatment and/or prophylaxis of diseases which can be treated with HDL-cholesterol raising agents, such as peripheral vascular disease, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, familial hypercholesterolemia, cardiovascular disorders, angina, ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension, and vascular complications of diabetes, obesity or endotoxemia.

  本发明涉及以下式子化合物的用途 其中 A、G、R1 至 R8 和 R17 如描述中所定义，用于制备治疗和/或预防可使用高密度脂蛋白胆固醇升高剂治疗的疾病的药物，如外周血管疾病、血脂异常、高脂蛋白血症、低脂蛋白血症、高胆固醇血症、高甘油三酯血症、家族性高胆固醇血症、心血管疾病、心绞痛、心肌缺血、高胆固醇血症、高甘油三酯血症、家族性高胆固醇血症、心血管疾病、心绞痛、心肌缺血、中风、心肌梗塞、再灌注损伤、血管再狭窄、高血压以及糖尿病、肥胖或内毒素血症的血管并发症。
• 2-PYRAZINECARBOXAMIDE DERIVATIVES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2035394A1

  公开（公告）日：2009-03-18