5,6-bis(4-bromophenyl)-pyrazine-2-carboxylic acid | 548760-11-8

• 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-bis(4-bromophenyl)-pyrazine-2-carboxylic acid
• 英文别名: 5,6-Bis-(4-bromophenyl)-pyrazine-2-carboxylic acid；5,6-bis(4-bromophenyl)pyrazine-2-carboxylic acid
• CAS: 548760-11-8
• 化学式: C₁₇H₁₀Br₂N₂O₂
• 分子量: 434.087
• InChiKey: TWOJMHLGDGWJPJ-UHFFFAOYSA-N

物化性质

• 沸点：
  517.5±50.0 °C(Predicted)
• 密度：
  1.726±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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-bis(4-bromophenyl)-pyrazine-2-carboxylic acid 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 三聚氯氰 、 sodium carbonate 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成
  参考文献：
  名称：

  组蛋白乙酰基转移酶P300 / CBP的组蛋白竞争性抑制剂的发现，构效关系和生物活性。

  摘要：

  组蛋白乙酰转移酶（HAT）p300及其旁系同源CBP乙酰化组蛋白赖氨酸侧链，在调节基因转录中起关键作用。p300 / CBP的HAT结构域是潜在的癌症药物靶标。通过化合物筛选和药物化学，发现了新的p300 / CBP HAT抑制剂，其IC50值低至620 nM。最有效的抑制剂与组蛋白底物竞争，对p300 / CBP表现出高选择性。它抑制细胞乙酰化，并具有1-3μM的EC50对几种肿瘤细胞系增殖的强活性。雌激素受体（ER）阳性乳腺癌MCF-7细胞中的基因表达谱表明，抑制剂治疗可概括siRNA介导的p300基因敲低，抑制ER介导的基因转录，并抑制了许多与癌症相关的基因签名的表达。这些结果表明，该抑制剂不仅是用于p300 / CBP HAT生物学研究的有用探针，而且还是用于进一步开发针对癌症的药物的药理学线索。

  DOI：

  10.1021/acs.jmedchem.9b02164
• 作为产物：
  描述：

  在 air 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 5,6-bis(4-bromophenyl)-pyrazine-2-carboxylic acid
  参考文献：
  名称：

  5,6-二芳基-吡嗪-2-酰胺衍生物的支架跳跃，合成和构效关系：一种新型的CB1受体拮抗剂。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2007.03.075

文献信息

• 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。
• 5, 6-diaryl-pyrazine-2-amide derivatives as CB1 antagonists
  申请人：AstraZeneca AB

  公开号：US07342019B2

  公开（公告）日：2008-03-11

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts, prodrugs, solvates and crystalline forms thereof, in which R1 and R2 independently represent: a C1-6alkyl group; an optionally substituted (amino)C1-4alkyl-group; an optionally substituted non-aromatic C3-15carbocyclic group; a (C3-12cycloalkyl)C1-3alkyl-group; a group —(CH2)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 —(CH2)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 R1 represents H and R2 is as defined above; or R1 and R2 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 SO2; Y is absent or represents NH optionally substitututed by a C1-3alkyl group; R3 and R4 independently represent phenyl, thienyl or pyridyl substituted by Z; Z represents a C1-3alkyl group, a C1-3alkoxy group, hydroxy, halo, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, trifluoromethylsulphonyl, nitro, amino, mono or di C1-3alkylamino, mono or di C1-3alkylamido, C1-3alkylsulphonyl, C1-3alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C1-3alkyl carbamoyl, sulphamoyl and acetyl; and R5 is H, a C1-3alkyl group, a C1-3alkoxymethyl group, trifluoromethyl, a hydroxyC1-3alkyl group, C1-3alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C1-3alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula —CONHNRaRb; 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.

  本发明涉及公式（I）的化合物，以及其药学上可接受的盐，前药，溶剂和晶体形式，其中R1和R2分别表示：C1-6烷基；一种可选取的取代（氨基）C1-4烷基基团；一种可选取的非芳香性C3-15碳环基团；一种（C3-12环烷基）C1-3烷基基团；一种—（CH2）r（苯基）s基团，其中r为0,1,2,3或4，当r为0时s为1，否则s为1或2，苯基可以是可选地独立取代的Z；萘基；蒽基；一种可选取的饱和5至8成员杂环基团，其中含有一个氮原子，可选地含有以下之一：氧，硫或另一个氮原子；1-金刚烷基甲基；一种—（CH2）t Het基团，其中t为0,1,2,3或4，烷基链可选地取代，Het表示可选地取代的芳香杂环；或R1表示H，R2如上定义；或R1和R2与它们连接的氮原子一起表示如上定义的饱和可选取代的5至8成员杂环基团；X为CO或SO2；Y不存在或表示可选地取代的C1-3烷基基团的NH；R3和R4分别表示可选地取代的Z取代的苯基，噻吩基或吡啶基；Z表示C1-3烷基基团，C1-3烷氧基基团，羟基，卤素，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，单个或双个C1-3烷基氨基，单个或双个C1-3烷基酰胺基，C1-3烷基磺酰基，C1-3烷氧羰基，羧基，氰基，氨基甲酰基，单个或双个C1-3烷基氨甲酰基，磺酰氨基和乙酰基；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，单个或双个C1-3烷基氨甲酰基，乙酰基或式为—CONHNRaRb的肼基羰基；具有以下条件和制备这些化合物的过程，其在肥胖症，精神和神经障碍的治疗中的用途，以及它们的治疗用途的方法和含有它们的制药组合物。
• 5,6-DIARYL-PYRAZINE-2-AMIDE DERIVATIVES AS CB1 ANTAGONISTS
  申请人：AstraZeneca AB

  公开号：EP1458690B1

  公开（公告）日：2007-02-21
• STABLE DISPERSION OF SOLID PARTICLES COMPRISING A WATER-INSOLUBLE PYRAZINE COMPOUND
  申请人：AstraZeneca AB

  公开号：EP1592451A1

  公开（公告）日：2005-11-09