N-methoxy-N-methyl-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide | 1047670-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-methoxy-N-methyl-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
• 英文别名: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid methoxy(methyl)amide；5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-methoxy-N,4-dimethylpyrazole-3-carboxamide
• CAS: 1047670-24-5
• 化学式: C₁₉H₁₆Cl₃N₃O₂
• 分子量: 424.714
• InChiKey: XKBVZERFDRDLAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methoxy-N-methyl-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以100%的产率得到5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxaldehyde
  参考文献：
  名称：

  Novel pyrazole derivatives as neutral CB 1 antagonists with significant activity towards food intake

  摘要：

  In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1, antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead 031 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((+/-)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(4-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.056
• 作为产物：
  描述：

  4-氯苯丙酮 在 三甲基铝 、 sodium 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 51.42h， 生成 N-methoxy-N-methyl-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Novel pyrazole derivatives as neutral CB 1 antagonists with significant activity towards food intake

  摘要：

  In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1, antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead 031 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((+/-)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(4-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.056

文献信息

• 1,5-Diaryl-Pyrazoles As Cannabinoid Receptor Neutral Antagonists Useful As Therapeutic Agents
  申请人：Greig Iain Robert

  公开号：US20100022611A1

  公开（公告）日：2010-01-28

  The present invention pertains to cannabinoid (CB) receptor neutral antagonists, and especially CB1 neutral antagonists, and including, for example, certain 1,5 -di-aryl-pyrazole compounds. The present invention also pertains to the use of such compounds in the treatment of diseases and disorders that are ameliorated by treatment with a neutral antagonist of the cannabinoid type 1 (CB1) receptor, for example: an eating disorder; obesity; a disease or disorder characterised by an addiction component; addiction; withdrawal; smoking addiction; smoking withdrawal; drug addiction; drug withdrawal; smoking cessation therapy; a bone disease or disorder; osteoporosis, Paget's disease of bone; bone related cancer; a disease or disorder with an inflammatory or autoimmune component; rheumatoid arthritis; inflammatory bowel disease; psoriasis; a psychiatric disease or disorder; anxiety; mania; schizophrenia; a disease or disorder characterised by impairment of memory and/or loss of cognitive function; memory impairment; loss of cognitive function; Parkinson's disease; Alzheimer's disease; dementia; a cardiovascular disease or disorder; congestive heart failure; cardiac hypertrophy; and myocardial infarction.

  本发明涉及大麻素（CB）受体中和拮抗剂，特别是CB1中和拮抗剂，包括例如某些1,5-二芳基吡唑化合物。本发明还涉及使用这些化合物治疗通过与大麻素类型1（CB1）受体的中和拮抗剂治疗改善的疾病和疾病，例如：进食障碍；肥胖症；以成瘾成分为特征的疾病或疾病；成瘾；戒断；吸烟成瘾；戒烟；药物成瘾；药物戒断；戒烟疗法；骨疾病或疾病；骨质疏松症，骨的帕吉特病；与骨有关的癌症；具有炎症或自身免疫成分的疾病或疾病；类风湿性关节炎；炎症性肠病；牛皮癣；精神疾病或疾病；焦虑症；狂躁症；精神分裂症；以记忆受损和/或认知功能丧失为特征的疾病或疾病；记忆障碍；认知功能丧失；帕金森病；阿尔茨海默病；痴呆；心血管疾病或疾病；充血性心力衰竭；心脏肥大；心肌梗塞。
• WO2008/99139
  申请人：——

  公开号：——

  公开（公告）日：——
• 1,5-DIARYL-PYRAZOLES AS CANNABINOID RECEPTOR NEUTRAL ANTAGONISTS USEFUL AS THERAPEUTIC AGENTS
  申请人：The University Court of The University of Aberdeen

  公开号：EP2125747A1

  公开（公告）日：2009-12-02
• [EN] 1,5-DIARYL-PYRAZOLES AS CANNABINOID RECEPTOR NEUTRAL ANTAGONISTS USEFUL AS THERAPEUTIC AGENTS<br/>[FR] 1,5-DIARYL-PYRAZOLES COMME ANTAGONISTES NEUTRES DES RÉCEPTEURS CANNABINOÏDES, UTILES COMME AGENTS THÉRAPEUTIQUES
  申请人：UNIV ABERDEEN

  公开号：WO2008099139A1

  公开（公告）日：2008-08-21

  [EN] The present invention pertains to cannabinoid (CB) receptor neutral antagonists, and especially CB1 neutral antagonists, and including, for example, certain 1,5-di-aryl-pyrazole compounds. The present invention also pertains to the use of such compounds in the treatment of diseases and disorders that are ameliorated by treatment with a neutral antagonist of the cannabinoid type 1 (CB1) receptor, for example: an eating disorder; obesity; a disease or disorder characterised by an addiction component; addiction; withdrawal; smoking addiction; smoking withdrawal; drug addiction; drug withdrawal; smoking cessation therapy; a bone disease or disorder; osteoporosis, Paget's disease of bone; bone related cancer; a disease or disorder with an inflammatory or autoimmune component; rheumatoid arthritis; inflammatory bowel disease; psoriasis; a psychiatric disease or disorder; anxiety; mania; schizophrenia; a disease or disorder characterised by impairment of memory and/or loss of cognitive function; memory impairment; loss of cognitive function; Parkinson's disease; Alzheimer's disease; dementia; a cardiovascular disease or disorder; congestive heart failure; cardiac hypertrophy; and myocardial infarction.
  [FR] La présente invention porte sur des antagonistes neutres des récepteurs cannabinoïdes (CB) et, en particulier, sur des antagonistes neutre des CB1, et comprenant, par exemple, certains composés 1,5-di-aryl-pyrazoles. La présente invention porte également sur l'utilisation de tels composés dans le traitement de maladies et troubles qui sont améliorés par le traitement par un antagoniste neutre des récepteurs cannabinoïdes de type 1 (CB1), par exemple : un trouble de l'alimentation ; l'obésité ; une maladie ou un trouble caractérisé par un composant d'addiction ; l'addiction ; le sevrage ; l'addiction à la cigarette ; le sevrage de la cigarette ; l'addiction aux médicaments ; le sevrage des médicaments ; la thérapie de cessation de fumer ; une maladie ou un trouble osseux ; l'ostéoporose ; la maladie de Paget de l'os ; le cancer apparenté à l'os ; une maladie ou un trouble avec un composant inflammatoire ou auto-immun ; l'arthrite rhumatoïde ; la maladie inflammatoire de l'intestin ; le psoriasis, une maladie ou un trouble psychiatrique ; l'anxiété ; la manie ; la schizophrénie ; une maladie ou un trouble caractérisé par l'affectation de la mémoire et/ou la perte de la fonction cognitive ; l'affectation de la mémoire ; la perte de fonction cognitive ; la maladie de Parkinson ; la maladie d'Alzheimer ; la démence ; une maladie ou un trouble cardiovasculaire ; la maladie cardiaque congestive ; l'hypertrophie cardiaque ; et l'infarctus du myocarde.
• Novel pyrazole derivatives as neutral CB 1 antagonists with significant activity towards food intake
  作者：Ilaria Manca、Andrea Mastinu、Francesca Olimpieri、Matteo Falzoi、Monica Sani、Stefania Ruiu、Giovanni Loriga、Alessandro Volonterio、Simone Tambaro、Mirko Emilio Heiner Bottazzi、Matteo Zanda、Gérard Aimè Pinna、Paolo Lazzari

  DOI：10.1016/j.ejmech.2012.12.056

  日期：2013.4

  In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1, antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead 031 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((+/-)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(4-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake. (C) 2013 Elsevier Masson SAS. All rights reserved.