5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxaldehyde | 913624-97-2

• 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-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxaldehyde
• 英文别名: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbaldehyde；1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazol-3-carbaldehyde；5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbaldehyde
• CAS: 913624-97-2
• 化学式: C₁₇H₁₁Cl₃N₂O
• 分子量: 365.646
• InChiKey: JKPASCAAHWDVFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxaldehyde 在 正丁基锂 、 potassium hydride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 19.0h， 生成 1-[2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-(Z)-vinyl]-piperidine
  参考文献：
  名称：

  大麻素CB1受体的Biarylpyrazole反向激动剂：C-3羧酰胺氧/赖氨酸3.28（192）相互作用的重要性。

  摘要：

  已显示联芳基吡唑，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（SR141716; 1）在大麻素CB1受体上起反向激动剂/拮抗剂的作用。我们之前的突变周期研究表明，K3.28（192）与野生型（WT）CB1中1的C-3取代基直接相互作用。（1）但是，这些结果并未确定1的C-3取代基与K3.28（192）氢键，羧酰胺氧或哌啶氮有关。此外，我们先前的5-（4-氯苯基）-3-[（E）-2-环己基乙烯基] -1-（2,4-二氯苯基）-4-甲基-1H-吡唑（VCHSR; 2 ）（1的类似物，其C-3取代基缺乏氢键能力）表明该化合物可作为中性拮抗剂，（1）这些结果表明联芳基吡唑与CB1处的K3.28（192）相互作用与反向激动作用之间存在一定的关系，但结果与1相反。单对化合物（1和2）。本文介绍的工作旨在测试从我们的建模和突变周期结果得出的两个假

  DOI：

  10.1021/jm060446b
• 作为产物：
  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

文献信息

• [EN] MMPL3 INHIBITORS, COMPOSITIONS AND USES THEREOF<br/>[FR] INHIBITEURS DE MMPL3, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV SHANGHAI TECH

  公开号：WO2020103856A1

  公开（公告）日：2020-05-28

  Disclosed are inhibitors of mycobacterial membrane protein MmpL3, compositions comprising the inhibitors, and methods of preparation and use thereof.

  揭示了抑制结核分枝杆菌膜蛋白MmpL3的抑制剂，包含这些抑制剂的组合物，以及其制备和使用方法。
• PYRAZOLE CARBOXAMIDE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND ITS PREPARATION
  申请人：Li Song

  公开号：US20100160383A1

  公开（公告）日：2010-06-24

  A compound of formula (I) or pharmaceutically acceptable salts and/or solvates or hydrates thereof. A process for preparing the compound, a pharmaceutical composition comprising the compound and an application for resisting cannabinoid CB1 receptor are provided.

  化合物的化学式(I)或其药学上可接受的盐和/或溶剂或水合物。提供了一种制备该化合物的方法，包括该化合物的药物组合物以及用于抵抗大麻素CB1受体的应用。
• [EN] 1,5-DIARYL-PYRAZOLES AND THEIR USE AS CANNABINOID RECEPTOR NEUTRAL ANTAGONISTS<br/>[FR] 1,5-DIARYL-PYRAZOLES ET LEUR UTILISATION COMME ANTAGONISTES NEUTRES DES RÉCEPTEURS CANNABINOÏDES
  申请人：UNIV ABERDEEN

  公开号：WO2010020762A1

  公开（公告）日：2010-02-25

  The present invention pertains to cannabinoid (CB) receptor and cannabinoid-like receptor neutral antagonists, and especially CB1 neutral antagonists of Formula (I). The present invention also pertains to these compounds for use in the treatment of diseases and disorders that are ameliorated by treatment with a neutral antagonist of the cannabinoid type 1 (CB1) receptor or a non-CB1/non-CB2 cannabinoid-like receptor, for example: an eating disorder; obesity; cardiovascular disease; 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; breast cancer; breast cancer metastases; breast cancer which has metastasised to bone; cancer associated with activation or inactivation of a non-CB1/non-CB2 cannabinoid-like receptor,

  本发明涉及大麻素（CB）受体和类大麻素受体中和拮抗剂，特别是公式（I）的CB1中和拮抗剂。本发明还涉及这些化合物在治疗通过使用大麻素类型1（CB1）受体的中和拮抗剂或非CB1/非CB2类大麻素受体得到改善的疾病和疾病的使用，例如：进食障碍；肥胖；心血管疾病；由成瘾成分特征的疾病或障碍；成瘾；戒断；吸烟成瘾；戒烟；药物成瘾；戒毒；戒烟疗法；骨骼疾病或障碍；骨质疏松症，Paget骨病；与激活或失活非CB1/非CB2类大麻素受体相关的癌症。
• Discovery of novel arylpyrazole series as potent and selective opioid receptor-like 1 (ORL1) antagonists
  作者：Kensuke Kobayashi、Minaho Uchiyama、Hirokatsu Ito、Hirobumi Takahashi、Takashi Yoshizumi、Hiroki Sakoh、Yasushi Nagatomi、Masanori Asai、Hiroshi Miyazoe、Tomohiro Tsujita、Mioko Hirayama、Satoshi Ozaki、Takeshi Tani、Yasuyuki Ishii、Hisashi Ohta、Osamu Okamoto

  DOI：10.1016/j.bmcl.2009.04.116

  日期：2009.7

  The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure–activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1H-pyrazol-3-yl]methyl}-3-fluorocyclopentanamine, which exhibits high intrinsic potency

  介绍了新型有效的阿片受体样1拮抗剂的合成和生物学评价。通过文库筛选获得的芳基吡唑铅化合物1的结构活性关系（SAR）研究确定了化合物31，（1 S，3 R）-N -[1-（3-氯吡啶-2-基）-5-（5 -氟-6-甲基吡啶基-3-基）-4-甲基-1 H-吡唑-3-基]甲基} -3-氟环戊胺，对其他阿片受体和hERG钾离子通道具有很高的内在效力和选择性。
• Design, synthesis and biological evaluation of CB1 cannabinoid receptor ligands derived from the 1,5-diarylpyrazole scaffold
  作者：GuoGang Tu、Fang Xiong、HuiMing Huang、BinHai Kuang、ShaoHua Li

  DOI：10.3109/14756366.2010.491794

  日期：2011.4.1

  The CB1 receptor belongs to the G-protein-coupled receptor superfamily. CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In this study, we report the synthesis and in vitro binding affinity assay of some 1,5-diarylpyrazole scaffold compounds. The binding results showed that some of the target compounds had an excellent potency toward the CB1 receptor with IC(50) values lying at the nanomole level.