3-(4-chlorophenyl)-N-{[isopropyl(methyl)amino]sulfonyl}-4-phenyl-4,5-dihydro-1 H-pyrazole-1-carbothioamide | 869278-58-0

• 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: 3-(4-chlorophenyl)-N-{[isopropyl(methyl)amino]sulfonyl}-4-phenyl-4,5-dihydro-1 H-pyrazole-1-carbothioamide
• 英文别名: 5-(4-chlorophenyl)-N-[methyl(propan-2-yl)sulfamoyl]-4-phenyl-3,4-dihydropyrazole-2-carbothioamide
• CAS: 869278-58-0
• 化学式: C₂₀H₂₃ClN₄O₂S₂
• 分子量: 451.013
• InChiKey: GBDFEQIOMVIYPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-N-{[isopropyl(methyl)amino]sulfonyl}-4-phenyl-4,5-dihydro-1 H-pyrazole-1-carbothioamide 、 甲胺 在 mercury dichloride 作用下， 反应 4.0h， 生成 5-(4-chlorophenyl)-N'-methyl-N-[methyl(propan-2-yl)sulfamoyl]-4-phenyl-3,4-dihydropyrazole-2-carboximidamide
  参考文献：
  名称：

  Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity

  摘要：

  Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffraction analysis and 24 showed a close molecular fit with rimonabant in a CB1 receptor-based model. Compound 17 exhibited the highest CB1 receptor affinity (K-i = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA(2) = 8.8) and a high CB1/CB2 subtype selectivity (similar to 147-fold). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.054
• 作为产物：
  描述：

  在 氯甲酸三氯甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 3-(4-chlorophenyl)-N-{[isopropyl(methyl)amino]sulfonyl}-4-phenyl-4,5-dihydro-1 H-pyrazole-1-carbothioamide
  参考文献：
  名称：

  Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity

  摘要：

  Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffraction analysis and 24 showed a close molecular fit with rimonabant in a CB1 receptor-based model. Compound 17 exhibited the highest CB1 receptor affinity (K-i = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA(2) = 8.8) and a high CB1/CB2 subtype selectivity (similar to 147-fold). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.054

文献信息

• Pharmaceutical compositions comprising CB1 cannabinoid receptor antagonists and potassium channel openers for the treatment of obesity and related conditions
  申请人：Firnges Michael

  公开号：US20060128673A1

  公开（公告）日：2006-06-15

  Described is a novel combination therapy for diabetes mellitus type I and/or for obesity and its concomitant and/or secondary diseases or conditions, in particular the metabolic syndrome and/or syndrome X, and/or diabetes mellitus type II, by administering a combination of at least one K ATP channel opener as a first active agent and at least one CB 1 cannabinoid receptor antagonist as a second active agent. The invention is further directed to such novel combination therapy wherein a dually acting compound with combined K ATP channel opening and CB 1 antagonistic properties is used. The invention also relates to novel pharmaceutical compositions comprising K ATP channel openers and CB 1 antagonists and the use of said pharmaceutical compositions in the treatment, delayed progression, delayed onset of and/or inhibition of diabetes mellitus type 1, and the prophylaxis and treatment, of obesity as well as the prophylaxis, treatment, delayed onset and/or inhbition of its concomitant and/or secondary diseases or conditions, in particular the metabolic syndrome and/or syndrome X, and/or diabetes mellitus type II, in mammals and humans. The invention is further directed to such novel pharmaceutical compositions comprising a dually acting compound with combined K ATP channel opening and CB 1 antagonistic properties.

  所述的是一种新型组合疗法，用于治疗 I 型糖尿病和/或肥胖症及其伴随和/或继发疾病或病症，特别是代谢综合征和/或 X 综合征和/或 II 型糖尿病，其方法是给药至少一种 K ATP 通道开启剂作为第一活性剂与至少一种 CB 1 大麻素受体拮抗剂作为第二活性制剂。本发明进一步涉及这种新型组合疗法，其中一种双重作用的化合物联合 K ATP 通道开放和 CB 1 拮抗特性的双重作用化合物。本发明还涉及包含 K ATP 通道开启剂和 CB 1 拮抗剂的新型药物组合物，以及将所述药物组合物用于治疗、延缓进展、延缓发病和/或抑制 1 型糖尿病，预防和治疗肥胖症，以及预防、治疗、延缓发病和/或抑制其伴随和/或继发疾病或病症，特别是哺乳动物和人类的代谢综合征和/或 X 综合征和/或 II 型糖尿病。本发明进一步涉及这种新型药物组合物，其中包含一种具有联合 K ATP 通道开放和 CB 1 拮抗特性的双重作用化合物。
• PHARMACEUTICAL COMPOSITIONS COMPRISING CB1 CANNABINOID RECEPTOR ANTAGONISTS AND POTASSIUM CHANNEL OPENERS FOR THE TREATMENT OF DIABETES MELLITUS TYPE I, OBESITY AND RELATED CONDITIONS
  申请人：Solvay Pharmaceuticals GmbH

  公开号：EP1807063A2

  公开（公告）日：2007-07-18
• US8058264B2
  申请人：——

  公开号：US8058264B2

  公开（公告）日：2011-11-15
• [EN] PHARMACEUTICAL COMPOSITIONS COMPRISING CB1 CANNABINOID RECEPTOR ANTAGONISTS AND POTASSIUM CHANNEL OPENERS FOR THE TREATMENT OF DIABETES MELLITUS TYPE I, OBESITY AND RELATED CONDITIONS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES CONTENANT DES ANTAGONISTES DES RECEPTEURS CANNABINOIDES ET DES AGENTS D'OUVERTURE DE CANAUX POTASSIQUES DANS LE TRAITEMENT DU DIABETE INSULINO-DEPENDANT, DE L'OBESITE ET DES ETATS ASSOCIES
  申请人：SOLVAY PHARM GMBH

  公开号：WO2006045799A2

  公开（公告）日：2006-05-04

  [EN] Described is a novel combination therapy for diabetes mellitus type I and/or for obesity and its concomitant and/or secondary diseases or conditions, in particular the metabolic syndrome and/or syndrome X, and/or diabetes mellitus type II, by administering a combination of at least one K_ATP channel opener as a first active agent and at least one CB1 cannabinoid receptor antagonist as a second active agent. The invention is further directed to such novel combination therapy wherein a dually acting compound with combined KATP channel opening and CB₁ antagonistic properties is used. The invention also relates to novel pharmaceutical compositions comprising K_ATP channel openers and CB1 antagonists and the use of said pharmaceutical compositions in the treatment, delayed progression, delayed onset of and/or inhibition of diabetes mellitus type I, and the prophylaxis and treatment, of obesity as well as the prophylaxis, treatment, delayed onset and/or inhibition of its concomitant and/or secondary diseases or conditions, in particular the metabolic syndrome and/or syndrome X, and/or diabetes mellitus type II, in mammals and humans. The invention is further directed to such novel pharmaceutical compositions comprising a dually acting compound with combined K_ATP channel opening and CB₁ antagonistic properties.
  [FR] L'invention concerne une nouvelle polythérapie destinée au traitement du diabète insulino-dépendant et/ou de l'obésité et de ses maladies ou états concomitants et/ou secondaires, en particulier le syndrome métabolique et/ou le syndrome X, et/ou du diabète de type 2, par l'administration d'une combinaison d'au moins un agent d'ouverture de canaux K_ATP comme premier principe actif et d'au moins un antagoniste des récepteurs cannabinoïdes CB₁ comme deuxième principe actif. L'invention concerne également une nouvelle polythérapie mettant en oeuvre un composé doublement actif présentant des propriétés d'ouverture de canaux K_ATP et des propriétés antagonistes CB₁ combinées. L'invention concerne encore de nouvelles compositions pharmaceutiques contenant des agents d'ouverture de canaux K_ATP et des antagonistes CB₁, ainsi que l'utilisation de ces compositions dans le traitement, le retardement de l'évolution, le retardement de l'apparition et/ou l'inhibition du diabète insulino-dépendant, et dans la prévention et le traitement de l'obésité, ainsi que dans la prévention, le traitement, le retardement de l'apparition et/ou l'inhibition de ses maladies ou états concomitants et/ou secondaires, en particulier le syndrome métabolique et/ou le syndrome X, et/ou le diabète de type 2, chez des mammifères et des humains. L'invention concerne enfin ces nouvelles compositions pharmaceutiques contenant un composé doublement actif présentant des propriétés d'ouverture de canaux K_ATP et des propriétés antagonistes CB₁ combinées.
• Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity
  作者：Jos H.M. Lange、Herman H. van Stuivenberg、Willem Veerman、Henri C. Wals、Bob Stork、Hein K.A.C. Coolen、Andrew C. McCreary、Tiny J.P. Adolfs、Chris G. Kruse

  DOI：10.1016/j.bmcl.2005.07.054

  日期：2005.11

  Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffraction analysis and 24 showed a close molecular fit with rimonabant in a CB1 receptor-based model. Compound 17 exhibited the highest CB1 receptor affinity (K-i = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA(2) = 8.8) and a high CB1/CB2 subtype selectivity (similar to 147-fold). (c) 2005 Elsevier Ltd. All rights reserved.