5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic chloride | 183232-64-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic chloride
• 英文别名: 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid chloride；5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbonyl chloride
• CAS: 183232-64-6
• 化学式: C₁₇H₁₀BrCl₃N₂O
• 分子量: 444.542
• InChiKey: RFVYHYSNXAXRNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic chloride 在 copper(l) iodide 、 palladium diacetate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 三乙胺 为溶剂， 反应 32.0h， 生成 1-(2,4-dichlorophenyl)-5-[4-(4-hydroxybut-1-ynyl)phenyl]-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide
  参考文献：
  名称：

  二价大麻素-1受体配体：SR141716A的连接子连接点研究，用于开发高亲和力的CB1R分子探针。

  摘要：

  大麻素1受体（CB1R）反向激动剂SR141716A已被证明可用于研究内源性大麻素系统，包括开发具有通过连接单元连接的第二个功能性基序的二价CB1R配体。这些主要使用中央吡唑环的C3位连接接头。尽管有这个先例，但是一系列新颖的C3连接的CB1R-D2R二价配体对D2R表现出极高的亲和力，但对CB1R的亲和力却很差。因此，对SR141716A药效团进行了系统的连接子连接点调查，确定了C5位置为连接子缀合的最佳位点。这项连接子附着调查使我们能够鉴定出一种新的二价配体作为先导化合物，以指导正在进行的高亲和力CB1R分子探针的开发。

  DOI：

  10.1016/j.bmcl.2019.126644
• 作为产物：
  描述：

  5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid 在 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic chloride
  参考文献：
  名称：

  吡唑衍生物作为大麻素受体拮抗剂的构效关系。

  摘要：

  作为一种有效的脑大麻素受体（CB1）拮抗剂，联芳吡唑N-（哌啶-1-基）-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基-1H -吡唑-3-甲酰胺（SR141716A; 1）是用于启动研究的主要化合物，旨在研究相关化合物的构效关系，并寻找更具选择性和效用的拟大麻素配体。设计并合成了一系列吡唑衍生物，以帮助表征大麻素受体结合位点，并用作潜在有用的药理探针。在治疗上，此类化合物可能具有拮抗大麻素和拟大麻剂的有害副作用的能力。有效和选择性的脑大麻素CB1受体拮抗活性的结构要求包括（a）在5位的对位取代苯环，（b）在3位的羧酰胺基和（c）2,4-二氯苯基在吡唑环的1-位上的取代基。该系列中最有效的化合物在吡唑环的5-位包含对碘苯基，在3-位包含哌啶基羧酰胺和在吡唑环的1-位包含2,4-二氯苯基。该化合物的碘化性质可作为富伽玛SPECT（单光子发射计算机断层扫描）配体，提供额外的实用性，可用

  DOI：

  10.1021/jm980363y

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：——
• Preparation of iodine-123 labeled AM251: A potential SPECT radioligand for the brain cannabinoid CB1 receptor
  作者：Ruoxi Lan、S. John Gatley、Alexandros Makriyannis

  DOI：10.1002/(sici)1099-1344(199610)38:10<875::aid-jlcr908>3.0.co;2-g

  日期：1996.10
• 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.
• 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