1-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid chloride | 158941-08-3

• 英文名称: 1-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid chloride
• 英文别名: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)pyrazole-3-carboxylic acid chloride；5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)pyrazole-3-carbonyl chloride
• CAS: 158941-08-3
• 化学式: C₁₆H₈Cl₄N₂O
• 分子量: 386.064
• InChiKey: QXVIJROYVBRASH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 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：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-氨基哌啶 、 1-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid chloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 NIDA 41119
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationship, and Evaluation of SR141716 Analogues:  Development of Central Cannabinoid Receptor Ligands with Lower Lipophilicity

  摘要：

  Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.

  DOI：

  10.1021/jm020157x
• 作为产物：
  描述：

  1-(2,4-二氯苯基)-5-(4-氯苯基)-1H-吡唑-3-羧酸 在 N,N-二甲基甲酰胺 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 1-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid chloride
  参考文献：
  名称：

  Discovery of Rimonabant and its potential analogues as anti-TB drug candidates

  摘要：

  Rimonabant and its analogues have been synthesized in moderate to good yields using a simple synthetic route. All the newly synthesized compounds were subjected to in vitro screening against M. tuberculosis and M. smegmatis. The most potent analogue JMG-14 exhibits MIC value of 3.13 compared to 3.25 and 50 A mu g/ml for ethambutol and pyrazinamide, respectively. The molecular docking reveals that pyrazole ring, number and position of halogen atoms play a crucial role in deciding interactions with MTCYP-121. These findings open up a new avenue in the search of potent anti-TB drugs with rimonabant and its novel analogue JMG-14 as lead molecules.

  DOI：

  10.1007/s00044-015-1346-4

文献信息

• Pyrazole-3-carboxamide derivatives, process for their preparation and
  申请人：Sanofi

  公开号：US05462960A1

  公开（公告）日：1995-10-31

  The present invention relates to novel pyrazole-3-carboxamide derivatives of the formula ##STR1## in which the substituents are as defined in the specification. The present invention further relates to a process for the preparation of these novel derivatives and to the pharmaceutical compositions in which they are present.

  本发明涉及一种新型的吡唑-3-羧酰胺衍生物，其化学式为##STR1##其中取代基如规范中定义。本发明还涉及一种制备这些新型衍生物的方法，以及它们存在的药物组合物。
• Discovery of 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1<i>H</i>-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an Active Metabolite. A Novel, Potent and Selective Cannabinoid-1 Receptor Inverse Agonist with High Antiobesity Efficacy in DIO Mice
  作者：Chien-Huang Wu、Ming-Shiu Hung、Jen-Shin Song、Teng-Kuang Yeh、Ming-Chen Chou、Cheng-Ming Chu、Jiing-Jyh Jan、Min-Tsang Hsieh、Shi-Liang Tseng、Chun-Ping Chang、Wan-Ping Hsieh、Yinchiu Lin、Yen-Nan Yeh、Wan-Ling Chung、Chun-Wei Kuo、Chin-Yu Lin、Horng-Shing Shy、Yu-Sheng Chao、Kak-Shan Shia

  DOI：10.1021/jm900471u

  日期：2009.7.23

  By using the active metabolite 5 as an initial template, further structural modifications led to the identification of the titled compound 24 (BPR-890) as a highly potent CB I inverse agonist possessing an excellent CB2/1 selectivity and remarkable in vivo efficacy in diet-induced obese mice with a minimum effective dose as low as 0.03 mg/kg (po qd) at the end of the 30-day chronic study. Current SAR studies along with those of many existing rimonabant-mimicking molecules imply that around the pyrazole C3-position, a rigid and deep binding pocket should exist for CB1 receptor. In addition, relative to the conventional carboxamide carbonyl, serving as a key hydrogen-bond acceptor during ligand-CB1 receptor interaction, the corresponding polarizable thione carbonyl might play a more critical role in stabilizing the Asp366-Lys192 salt bridge in the proposed CB1-receptor homology model and inducing significant selectivity for CB1R over CB2R.
• US5462960A
  申请人：——

  公开号：US5462960A

  公开（公告）日：1995-10-31
• US5624941A
  申请人：——

  公开号：US5624941A

  公开（公告）日：1997-04-29
• [EN] NOVEL FORMS OF RIMONABANT<br/>[FR] NOUVELLES FORMES DU RIMONABANT
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2008056377A2

  公开（公告）日：2008-05-15

  [EN] Disclosed herein are the novel amorphous hydrated and crystalline forms of Rimonabant, process(s) for their preparation and pharmaceutical compositions containing it.
  [FR] La présente invention concerne les nouvelles formes hydratées et cristallines amorphes du Rimonabant, un ou plusieurs procédés de préparation de ces nouvelles formes, ainsi que des compositions pharmaceutiques contenant ces nouvelles formes.