ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylsulfanyl-1H-pyrazole-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylsulfanyl-1H-pyrazole-3-carboxylate
• 英文别名: ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(methylthio)-1H-pyrazole-3-carboxylate；ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylsulfanylpyrazole-3-carboxylate
• 化学式: C₁₉H₁₅Cl₃N₂O₂S
• 分子量: 441.765
• InChiKey: RAOUZEAZFOSBGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylsulfanyl-1H-pyrazole-3-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以70%的产率得到5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(methylthio)-1H-pyrazole-3-carbohydrazide
  参考文献：
  名称：

  [EN] SULFUR CONTAINING PYRAZOLE-HETEROCYCLE DERIVATIVES AS CANNABINOID CB1 RECEPTOR ANTAGONISTS
  [FR] DÉRIVÉS DE TYPE PYRAZOLE-HÉTÉROCYCLE CONTENANT DU SOUFRE EN TANT QU'ANTAGONISTES DES RÉCEPTEURS CANNABINOÏDES CB1

  摘要：

  一种含硫杂环吡唑化合物的新型化合物，其化学式为（I），或其药用可接受的盐，作为大麻素CB1受体的反向激动剂或拮抗剂具有良好效果，可用于预防或治疗肥胖和与肥胖相关的代谢紊乱。该预防方法还提供了一种制备该化合物的方法，含有该化合物的药物组合物，以及预防或治疗肥胖和与肥胖相关的代谢紊乱的方法。

  公开号：

  WO2010035915A1
• 作为产物：
  描述：

  ω-(Methylthio)-p-chloroacetophenone 在 lithium hexamethyldisilazane 作用下， 以 乙醇 、 甲基叔丁基醚 为溶剂， 反应 18.5h， 生成 ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylsulfanyl-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  SULFUR CONTAINING PYRAZOLE-HETEROCYCLE DERIVATIVES AS CANNABINOID CB1 RECEPTOR ANTAGONISTS

  摘要：

  一种含硫杂环吡唑烷化合物，化学式为(I)，或其药学上可接受的盐，作为一种大麻素CB1受体的反向激动剂或拮抗剂具有有效性，可用于预防或治疗肥胖和与肥胖相关的代谢性疾病。该预防方法还提供了一种制备相同的方法，含有相同的药物组合物，以及预防或治疗肥胖和与肥胖相关的代谢性疾病的方法。

  公开号：

  US20110178140A1

文献信息

• SULPHUR CONTAINING PYRAZOLE DERIVATIVES AS SELECTIVE CANNABINOID CB1 RECEPTOR ANTAGONISTS
  申请人：Lange Josephus H.M.

  公开号：US20070281973A1

  公开（公告）日：2007-12-06

  The present invention relates to sulphur containing pyrazole derivatives, and their S-oxidized active metabolites, as selective cannabinoid CB 1 receptor antagonists having a high CB 1 /CB 2 receptor subtype selectivity, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of these pyrazole derivatives, to pharmaceutical compositions comprising one or more of these pyrazole derivatives as active ingredients, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

  本发明涉及含硫吡唑衍生物及其S-氧化活性代谢物，作为具有高CB1/CB2受体亚型选择性的选择性大麻素CB1受体拮抗剂，以及制备这些化合物的方法，用于合成这些吡唑衍生物的新型中间体，包含一种或多种这些吡唑衍生物作为活性成分的药物组合物，以及这些药物组合物用于治疗精神疾病和神经疾病的用途。这些化合物具有通式（I），其中符号的含义如规范中所述。
• Sulphur containing pyrazole derivatives as selective cannabinoid CB1 receptor antagonists
  申请人：Solvay Pharmaceuticals B.V.

  公开号：US07786144B2

  公开（公告）日：2010-08-31

  The present invention relates to sulphur containing pyrazole derivatives, and their S-oxidized active metabolites, as selective cannabinoid CB1 receptor antagonists having a high CB1/CB2 receptor subtype selectivity, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of these pyrazole derivatives, to pharmaceutical compositions comprising one or more of these pyrazole derivatives as active ingredients, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

  本发明涉及含硫的吡唑衍生物及其S-氧化活性代谢物，作为具有高CB1/CB2受体亚型选择性的选择性大麻素CB1受体拮抗剂，以及制备这些化合物的方法，用于合成这些吡唑衍生物的新型中间体，包含一种或多种这些吡唑衍生物作为活性成分的制药组合物，以及利用这些制药组合物治疗精神和神经系统疾病的用途。这些化合物的一般式为（I），其中符号的含义在规范中给出。
• Sulfur containing pyrazole-heterocycle derivatives as cannabinoid CB1 receptor antagonists
  申请人：Green Cross Corporation

  公开号：US08309584B2

  公开（公告）日：2012-11-13

  A novel sulfur containing heteroaryl-pyrazole compound of formula (I) or a pharmaceutically acceptable salt thereof is effective as a cannabinoid CB1 receptor inverse agonist or antagonist, which is useful for preventing or treating obesity and obesity-related metabolic disorders. The prevention also provide a method for preparing same, a pharmaceutical composition containing same, and a method for preventing or treating obesity and obesity-related metabolic disorders.

  化合物(I)或其药学上可接受的盐，是一种含硫杂环吡唑化合物，可作为大麻素CB1受体的反向激动剂或拮抗剂，对预防或治疗肥胖和肥胖相关代谢紊乱有效。本发明还提供了制备该化合物的方法，包含该化合物的制剂组合物，以及预防或治疗肥胖和肥胖相关代谢紊乱的方法。
• Sulphur containing pyrazole derivatives as selective cannabinoid CB1 receptor antagonists
  申请人：Lange Josephus H. M.

  公开号：US08461184B2

  公开（公告）日：2013-06-11

  The present invention relates to sulphur containing pyrazole derivatives, and their S-oxidized active metabolites, as selective cannabinoid CB1 receptor antagonists having a high CB1/CB2 receptor subtype selectivity, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of these pyrazole derivatives, to pharmaceutical compositions comprising one or more of these pyrazole derivatives as active ingredients, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

  本发明涉及含硫吡唑衍生物及其S-氧化的活性代谢物，作为高CB1/CB2受体亚型选择性的选择性大麻素CB1受体拮抗剂，以及制备这些化合物的方法，用于合成这些吡唑衍生物的新型中间体，包含一种或多种这些吡唑衍生物作为活性成分的制药组合物，以及将这些制药组合物用于治疗精神和神经疾病的用途。这些化合物具有通式(I)，其中符号在规范中给出。
• Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern
  作者：Jos H.M. Lange、Martina A.W. van der Neut、Alice J.M. Borst、Mahmut Yildirim、Herman H. van Stuivenberg、Bernard J. van Vliet、Chris G. Kruse

  DOI：10.1016/j.bmcl.2010.03.068

  日期：2010.5

  The cannabinoid CB1/CB2 receptor subtype selectivity in the 1,2-diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5-substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than similar to 840-fold CB1/CB2 subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB1-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21. (C) 2010 Elsevier Ltd. All rights reserved.