5,6-di-p-tolyl-pyrazine-2-carboxylic acid | 548760-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5,6-di-p-tolyl-pyrazine-2-carboxylic acid
• 英文别名: 5,6-Bis(4-methylphenyl)pyrazine-2-carboxylic acid
• CAS: 548760-12-9
• 化学式: C₁₉H₁₆N₂O₂
• 分子量: 304.348
• InChiKey: VYVFAXPWSMCZTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-di-p-tolyl-pyrazine-2-carboxylic acid 在 草酰氯 、 PS-DIEA 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-ethyl-5,6-dip-tolylpyrazine-2-carboxamide
  参考文献：
  名称：

  Discovery of pyrazine carboxamide CB1 antagonists: The introduction of a hydroxyl group improves the pharmaceutical properties and in vivo efficacy of the series

  摘要：

  Structure-activity relationships for a series of pyrazine carboxamide CB1 antagonists are reported. Pharmaceutical properties of the series are improved via inclusion of hydroxyl-containing sidechains. This structural modification sufficiently improved ADME properties of an orally inactive series such that food intake reduction was achieved in rat feeding models. Compound 35 elicits a 46% reduction in food intake in ad libidum fed rats 4-h post-dose. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.087
• 作为产物：
  描述：

  Methyl 5,6-bis-(4-methylphenyl)pyrazin-2-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 5,6-di-p-tolyl-pyrazine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of pyrazine carboxamide CB1 antagonists: The introduction of a hydroxyl group improves the pharmaceutical properties and in vivo efficacy of the series

  摘要：

  Structure-activity relationships for a series of pyrazine carboxamide CB1 antagonists are reported. Pharmaceutical properties of the series are improved via inclusion of hydroxyl-containing sidechains. This structural modification sufficiently improved ADME properties of an orally inactive series such that food intake reduction was achieved in rat feeding models. Compound 35 elicits a 46% reduction in food intake in ad libidum fed rats 4-h post-dose. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.087

文献信息

• Scaffold hopping, synthesis and structure–activity relationships of 5,6-diaryl-pyrazine-2-amide derivatives: A novel series of CB1 receptor antagonists
  作者：Jonas Boström、Kristina Berggren、Thomas Elebring、Peter J. Greasley、Michael Wilstermann

  DOI：10.1016/j.bmc.2007.03.075

  日期：2007.6

  A scaffold hopping approach has been exploited to design a novel class of cannabinoid (CB1) receptor antagonists for the treatment of obesity. On the basis of shape-complementarity and synthetic feasibility the central fragment, a methylpyrazole, in Rimonabant was replaced by a pyrazine. The synthesis and CB1 antagonistic activities of a new series of 5,6-diaryl-pyrazine-2-amide derivatives are described

  已经开发出一种支架跳跃方法来设计用于治疗肥胖症的新型大麻素（CB1）受体拮抗剂。基于形状互补性和合成可行性，利莫那班的中心片段甲基吡唑被吡嗪取代。描述了一系列新的5,6-二芳基-吡嗪-2-酰胺衍生物的合成和CB1拮抗活性。几种化合物对CB1受体的拮抗药效力低于10nM。
• Stable dispersion of solid particles comprising a water-insoluble pyrazine compound
  申请人：Lindfors Lennart

  公开号：US20060134146A1

  公开（公告）日：2006-06-22

  A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a pyrazine compound of Formula I, a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions prepared by the process, solid particles prepared by the process and use of such particles.

  一种制备稳定固体颗粒分散液的方法，其中包括将（a）第一溶液与（b）水相结合，从而沉淀出包含抑制剂和基本上不溶于水的Formula I吡嗪化合物的固体颗粒，所述第一溶液包括基本上不溶于水的物质、水相溶的有机溶剂和抑制剂，可选地还包括稳定剂；并可选地去除水相溶的有机溶剂；其中所述抑制剂是描述中定义的非聚合疏水有机化合物。此外，还声明了通过该方法制备的稳定分散液、通过该方法制备的固体颗粒以及使用这些颗粒的用途。
• 5 6-diaryl-pyrazine-2-amide derivatives as cb1 antagonists
  申请人：Berggren Ingrid Kristina Anna

  公开号：US20050032808A1

  公开（公告）日：2005-02-10

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts, prodrugs, solvates and crystalline forms thereof, in which R 1 and R 2 independently represent: a C 1-6 alkyl group; an optionally substituted (amino)C 1-4 alkyl-group; an optionally substituted non-aromatic C 3-15 carbocyclic group; a (C 3-12 cycloalkyl)C 1-3 alkyl-group; a group —(CH 2 ) r (phenyl) s in which r is 0, 1, 2, 3 or 4, s is 1 when r is 0 otherwise s is 1 or 2 and the phenyl groups are optionally independently substituted by Z; naphthyl; anthracenyl; an optionally substituted saturated 5 to 8 membered heterocyclic group containing one nitrogen and optionally one of the following: oxygen, sulphur or an additional nitrogen; 1-adamantylmethyl; a group —(CH 2 ) t Het in which t is 0, 1, 2, 3 or 4, and the alkylene chain is optionally substituted and Het represents an optionally substituted aromatic heterocycle; or R 1 represents H and R 2 is as defined above; or R 1 and R 2 together with the nitrogen atom to which they are attached represent a saturated optionally substituted 5 to 8 membered heterocyclic group as defined above; X is CO or SO 2 ; Y is absent or represents NH optionally substitututed by a C 1-3 alkyl group; R 3 and R 4 independently represent phenyl, thienyl or pyridyl substituted by Z; Z represents a C 1-3 alkyl group, a C 1-3 alkoxy group, hydroxy, halo, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, trifluoromethylsulphonyl, nitro, amino, mono or di C 1-3 alkylamino, mono or di C 1-3 alkylamido, C 1-3 alkylsulphonyl, C 1-3 alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C 1-3 alkyl carbamoyl, sulphamoyl and acetyl; and R 5 is H, a C 1-3 alkyl group, a C 1-3 alkoxymethyl group, trifluoromethyl, a hydroxyC 1-3 alkyl group, C 1-3 alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C 1-3 alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula —CONHNR a R b ; with the provisos; and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  本发明涉及化合物(I)及其药学上可接受的盐、前药、溶剂和晶体形式，其中R1和R2分别代表：C1-6烷基；可选地取代的（氨基）C1-4烷基基团；可选地取代的非芳香性C3-15环烷基团；（C3-12环烷基）C1-3烷基基团；—（CH2）r（苯基）s，其中r为0、1、2、3或4，s为1时r为0，否则s为1或2，苯基可以独立地被Z取代；萘基；蒽基；可选地取代的饱和的5至8元杂环基团，其中包含一个氮和可选的以下之一：氧、硫或另一个氮；1-金刚烷基甲基；—（CH2）tHet，其中t为0、1、2、3或4，烷基链可选地被取代，Het代表可选地取代的芳香杂环；或R1代表H，R2如上所定义；或R1和R2与它们连接的氮原子一起表示如上所定义的饱和可选地取代的5至8元杂环基团；X为CO或SO2；Y不存在或代表可选地取代的C1-3烷基基团的NH；R3和R4分别表示被Z取代的苯基、噻吩基或吡啶基；Z代表C1-3烷基基团、C1-3烷氧基基团、羟基、卤、三氟甲基、三氟甲硫基、三氟甲氧基、三氟甲基磺酰基、硝基、氨基、单或双C1-3烷基氨基、单或双C1-3烷基酰胺基、C1-3烷基磺酰基、C1-3烷氧基羰基、羧基、氰基、氨基甲酰基、单或双C1-3烷基氨基甲酰基、磺酰胺基和乙酰基；R5为H、C1-3烷基基团、C1-3烷氧甲基基团、三氟甲基、羟基C1-3烷基基团、C1-3烷氧羰基、羧基、氰基、氨基甲酰基、单或双C1-3烷基氨基甲酰基、乙酰基或公式—CONHNRaRb的肼基，其中Ra和Rb分别为H或C1-3烷基；但需要注意的是，本发明还涉及制备这些化合物的方法、它们在肥胖症、精神和神经疾病治疗中的用途以及含有它们的制药组合物。
• Pyrazine modulators of cannabinoid receptors
  申请人：Ellsworth A. Bruce

  公开号：US20050054659A1

  公开（公告）日：2005-03-10

  The present application describes compounds according to Formula I, wherein A, G 1 , G 2 and R 1 are described herein. Additionally, the present application describes pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents. Finally, the present application describes methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents.

  本申请描述了按照公式I的化合物，其中A、G1、G2和R1的定义在此处描述。此外，本申请还描述了包含至少一种按照公式I的化合物和可选的一种或多种额外治疗剂的制药组合物。最后，本申请还描述了使用按照公式I的化合物单独或与一种或多种额外治疗剂联合使用的治疗方法。
• 3-Substituted 5,6-diaryl-pyrazine-2-carboxamide and -2-sulfonamide derivatives as cb1 modulators
  申请人：Cheng Leifeng

  公开号：US20070093484A1

  公开（公告）日：2007-04-26

  The present invention relates to 3-substituted-5,6-diarylpyrazine-2-carboxamide and -2-sulfonamide compounds and their compositions, processes for their preparation, and their use in the treatment of obesity and psychiatric and neurological disorders.

  本发明涉及3-取代-5,6-二芳基吡嗪-2-羧酰胺和-2-磺酰胺化合物及其组合物，其制备过程以及它们在治疗肥胖症和精神和神经障碍方面的用途。