1-(4-methylbenzyl)-5-(4-chloro-3-methylphenyl)pyrazole-3-carboxylic acid chloride | 192703-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-methylbenzyl)-5-(4-chloro-3-methylphenyl)pyrazole-3-carboxylic acid chloride
• 英文别名: 5-(4-Chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carbonyl chloride；5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]pyrazole-3-carbonyl chloride
• CAS: 192703-20-1
• 化学式: C₁₉H₁₆Cl₂N₂O
• 分子量: 359.255
• InChiKey: YOXHQFIXVVNHIE-UHFFFAOYSA-N

物化性质

• 沸点：
  515.5±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  24
• 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：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-亚甲二氧基苄胺 、 1-(4-methylbenzyl)-5-(4-chloro-3-methylphenyl)pyrazole-3-carboxylic acid chloride 在 乙酸乙酯 、 碳酸氢钠 、 氯化钠 、 Sodium sulfate-III 作用下， 以 二氯甲烷 、 三乙胺 为溶剂， 反应 16.0h， 生成 5-(4-Chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxylic acid (benzo[1,3]dioxol-5-yl-methyl) amide
  参考文献：
  名称：

  Cannabinoid receptor inverse agonists and neutral antagonists as therapeutic agents for the treatment of bone disorders

  摘要：

  本发明涉及大麻素（CB）受体的反向激动剂和中性拮抗剂，尤其是CB1和CB2的反向激动剂和中性拮抗剂，例如某些吡唑化合物；它们用于抑制破骨细胞（例如抑制破骨细胞的存活、形成和/或活动），和/或抑制骨吸收；它们用于治疗骨疾病，例如由破骨细胞介导的疾病（例如破骨细胞活性增加）和/或以（例如增加的）骨吸收为特征的疾病，例如骨质疏松症（例如与炎症无关的骨质疏松症；例如与遗传倾向、性激素缺乏或衰老有关的骨质疏松症）、癌症相关骨疾病和Paget骨病。

  公开号：

  US20060172019A1
• 作为产物：
  描述：

  4-(4-氯-3-甲基苯基)-2,4-二氧代丁酸乙酯 在 氯化亚砜 作用下， 生成 1-(4-methylbenzyl)-5-(4-chloro-3-methylphenyl)pyrazole-3-carboxylic acid chloride
  参考文献：
  名称：

  Tritiation of the cannabinoid receptor antagonist SR144528 involving lithium aluminum tritide reduction; assessment of the kinetic isotope effect by3H-NMR

  摘要：

  大麻素受体拮抗剂SR144528的合成采用了一种方法，该方法能够在避免目标化合物对催化加氢的敏感性的情况下，准确纳入高比活性的氚标签。使用的锂铝氚化物的比活性低于最大比活性，以引入氚，导致氢/氚的引入表明在甲基苯甲酸酯的氢化/氚化还原过程中没有动力学同位素效应。版权 © 2005 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.952

文献信息

• The Importance of Hydrogen Bonding and Aromatic Stacking to the Affinity and Efficacy of Cannabinoid Receptor CB₂ Antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-<i>N</i>-[(1<i>S</i>,2<i>S</i>,4<i>R</i>)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528)
  作者：Evangelia Kotsikorou、Frank Navas、Michael J. Roche、Anne F. Gilliam、Brian F. Thomas、Herbert H. Seltzman、Pritesh Kumar、Zhao-Hui Song、Dow P. Hurst、Diane L. Lynch、Patricia H. Reggio

  DOI：10.1021/jm400070u

  日期：2013.9.12

  Despite the therapeutic promise of the subnanomolar affinity cannabinoid CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphe nyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicydo [2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528, 1), little is known about its binding site interactions and no primary interaction site for 1 at CB2 has been identified. We report here the results of Glide docking studies in our cannabinoid CB2 inactive state model that were then tested via compound synthesis, binding, and functional assays. Our results show that the amide functional group of 1 is critical to its CB2 affinity and efficacy and that aromatic stacking interactions in the TMH5/6 aromatic cluster of CB2 are also important. Molecular modifications that increased the positive electrostatic potential in the region between the fenthyl and aromatic rings led to more efficacious compounds. This result is consistent with the EC-3 loop negatively charged amino acid, D275 (identified via Glide docking studies) acting as the primary interaction site for 1 and its analogues.
• CANNABINOID RECEPTOR INVERSE AGONISTS AND NEUTRAL ANTAGONISTS AS THERAPEUTIC AGENTS FOR THE TREATMENT OF BONE DISORDERS
  申请人：The University Court of The University of Aberdeen

  公开号：EP1606019A1

  公开（公告）日：2005-12-21
• US5925768A
  申请人：——

  公开号：US5925768A

  公开（公告）日：1999-07-20
• [EN] CANNABINOID RECEPTOR INVERSE AGONISTS AND NEUTRAL ANTAGONISTS AS THERAPEUTIC AGENTS FOR THE TREATMENT OF BONE DISORDERS<br/>[FR] AGONISTES INVERSES DE RECEPTEURS DE CANNABINOIDES ET ANTAGONISTES NEUTRES AGISSANT EN TANT QU'AGENTS THERAPEUTIQUES DESTINES AU TRAITEMENT DE TROUBLES OSSEUX
  申请人：UNIV ABERDEEN

  公开号：WO2004078261A1

  公开（公告）日：2004-09-16

  The present invention pertains to cannabinoid (CB) receptor inverse agonists and neutral antagonists, and especially CB1 and CB2 inverse agonists and neutral antagonists; such as, for example, certain pyrazole compounds; their use in the inhibition of osteoclasts (for example, the inhibition of the survival, formation, and/or activity of osteoclasts), and/or in the inhibition of bone resorption; their use in connection with treatment of bone disorders, such as conditions mediated by osteoclasts (e.g., increased osteoclast activity) and/or characterised by (e.g., increased) bone resorption, such as osteoporosis (e.g., osteoporosis not associated with inflammation; e.g., osteoporosis associated with a genetic predisposition, sex hormone deficiency, or ageing), cancer associated bone disease, and Paget's disease of bone.