1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)ethane-1,2-dione | 489447-65-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)ethane-1,2-dione
• CAS: 489447-65-6
• 化学式: C₁₄H₇Cl₃O₂
• 分子量: 313.567
• InChiKey: JEHBJHIEQNHRKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)ethane-1,2-dione 、 2,3-二氨基丙酸 在 sodium hydroxide 、 air 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrazine-2-carboxylic acid 、 6-(4-chlorophenyl)-5-(2,4-dichlorophenyl)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
• 作为产物：
  描述：

  1-(4-chlorophenyl)-3-(2,4-dichlorophenyl)-2-propen-1-one 在 copper(II) nitrate trihydrate 、 potassium acetate 、 溶剂黄146 、 sodium iodide 作用下， 反应 9.0h， 以66%的产率得到1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)ethane-1,2-dione
  参考文献：
  名称：

  Copper-mediated aerobic oxidative cleavage of α,β-unsaturated ketones to 1,2-diketones

  摘要：

  描述了一种铜介导的有氧氧化裂解α,β-不饱和酮合成1,2-二酮的方法，该方法使用醋酸钾作为催化剂，碘化钠作为促进剂，在醋酸中进行。该方案的优点是使用便宜且无毒的原材料，产率高且操作步骤简单。

  DOI：

  10.1039/c4ra05307a

文献信息

• Substituted imidazoles as cannabinoid receptor modulators
  申请人：——

  公开号：US20030114495A1

  公开（公告）日：2003-06-19

  The use of compounds of the present invention as antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor particularly in the treatment, prevention and suppression of diseases mediated by the Cannabinoid-1 (CB1) receptor. The invention is concerned with the use of these novel compounds to selectively antagonize the Cannabinoid-1 (CB1) receptor. As such, compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, particularly to opiates, alcohol, and nicotine. The compounds are also useful for the treatment of obesity or eating disorders associated with excessive food intake and complications associated therewith. Novel compounds of structural formula (I) are also claimed.

  本发明涉及将这些新型化合物用于选择性拮抗Cannabinoid-1（CB1）受体。因此，本发明的化合物可用作治疗精神病、记忆障碍、认知障碍、偏头痛、神经病、神经炎症性疾病（包括多发性硬化症和吉兰-巴雷综合征）、病毒性脑炎、脑血管意外和头部创伤的炎症后遗症、焦虑症、压力、癫痫、帕金森病和精神分裂症的精神药物。这些化合物还可用于治疗物质滥用障碍，特别是阿片类药物、酒精和尼古丁。这些化合物还可用于治疗与过度食物摄入及相关并发症相关的肥胖或进食障碍。同时还声明了结构式（I）的新型化合物。
• 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。
• One-pot synthesis of unsymmetrical benzils and N-heteroarenes through nucleophilic aroylation catalyzed by N-heterocyclic carbene
  作者：Yumiko Suzuki、Mai Murofushi、Kei Manabe

  DOI：10.1016/j.tet.2012.11.039

  日期：2013.1

  An efficient one-pot synthesis of various unsymmetrical benzils via N-heterocyclic carbene (NHC)-catalyzed aroylation of N-phenylimidoyl chlorides with aromatic aldehydes followed by acidic hydrolysis has been developed. The one-pot procedure was extended to synthesis of quinoxalines and pyrazines by condensation/annulation of unsymmetrical benzils generated in situ with diamines. Crown Copyright (c) 2012 Published by Elsevier Ltd. All rights reserved.