5,6-Bis(4-chlorophenyl)-n-piperidin-1-ylpyrazine-2-carboxamide | 548759-96-2

• 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-chlorophenyl)-n-piperidin-1-ylpyrazine-2-carboxamide
• CAS: 548759-96-2
• 化学式: C₂₂H₂₀Cl₂N₄O
• 分子量: 427.333
• InChiKey: FBMFLCCMSCORDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5,6-bis(4-chlorophenyl)-pyrazine-2-carboxylic acid 、 1-氨基哌啶 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以15%的产率得到5,6-Bis(4-chlorophenyl)-n-piperidin-1-ylpyrazine-2-carboxamide
  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。
• Process for the preparation of crystalline nano-particle dispersions
  申请人：Skantze Urban Tommy

  公开号：US20050202092A1

  公开（公告）日：2005-09-15

  A process for the preparation of a dispersion of crystalline nano-particles in an aqueous medium comprising combining (i) a first solution comprising a substantially water-insoluble substance in a water-miscible organic solvent with; (ii) an aqueous phase comprising water and optionally a stabiliser, to form a dispersion of amorphous particles; and (iii) sonicating the dispersion of amorphous particles for a sufficient period to form crystalline nano-particles of the substantially water-insoluble substance. The process provides nano-crystals with a mean hydrodynamic diameter of less than 1 micron, particularly less than 300 nm and is particularly useful for the preparation of nano-crystalline dispersions of pharmaceutical substances.

  一种在水介质中制备结晶纳米颗粒分散液的工艺，包括将(i)第一溶液（包括在水可混溶的有机溶剂中的基本不溶于水的物质）与(ii)水相（包括水和可选的稳定剂）相结合，以形成无定形颗粒分散液；以及(iii)将无定形颗粒分散液超声足够长的时间，以形成基本不溶于水的物质的结晶纳米颗粒。该工艺提供的纳米晶体的平均水动力直径小于 1 微米，特别是小于 300 纳米，特别适用于制备药物物质的纳米晶体分散体。
• 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
• PROCESS FOR THE PREPARATION OF CRYSTALLINE NANO-PARTICLE DISPERSIONS
  申请人：AstraZeneca AB

  公开号：EP1524964A1

  公开（公告）日：2005-04-27