4-(4-(1-(2,4-dichlorophenyl)-4-methyl-3-(piperidin-1-ylcarbamoyl)-1H-pyrazol-5-yl)phenyl)but-3-yn-1-yl nitrate | 1245626-00-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-(1-(2,4-dichlorophenyl)-4-methyl-3-(piperidin-1-ylcarbamoyl)-1H-pyrazol-5-yl)phenyl)but-3-yn-1-yl nitrate
• 英文别名: AM6538；4-[4-[2-(2,4-Dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl]but-3-ynyl nitrate
• CAS: 1245626-00-9
• 化学式: C₂₆H₂₅Cl₂N₅O₄
• 分子量: 542.422
• InChiKey: KXXKUWQMQUYUSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2,4-dichlorophenyl)-5-(4-(4-iodobut-1-ynyl)phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide 在 silver nitrate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以65%的产率得到4-(4-(1-(2,4-dichlorophenyl)-4-methyl-3-(piperidin-1-ylcarbamoyl)-1H-pyrazol-5-yl)phenyl)but-3-yn-1-yl nitrate
  参考文献：
  名称：

  人类大麻素受体CB1的晶体结构。

  摘要：

  大麻素受体1（CB 1）是Δ的主要目标9四氢大麻酚（THC），从大麻一个精神化学具有广泛的治疗性应用和娱乐用途的很长的历史。CB 1被内源性大麻素激活，是治疗疼痛，炎症，肥胖和药物滥用疾病的有希望的治疗靶标。在这里，我们提出了与C6稳定剂AM6538结合的人CB 1的2.8Å晶体结构，并对其进行了结构表征。CB 1的结构-AM6538复合物揭示了受体的关键特征以及与拮抗剂结合的关键相互作用。结合功能研究和分子建模，该结构提供了对天然存在的CB 1配体（如THC）和合成大麻素的结合模式的深入了解。这增强了我们对CB 1生理功能的分子基础的理解，并为设计下一代CB 1靶向药物提供了新的机会。

  DOI：

  10.1016/j.cell.2016.10.004

文献信息

• [EN] NOVEL HETERO PYRROLE ANALOGS ACTING ON CANNAPINOID RECEPTORS<br/>[FR] NOUVEAUX ANALOGUES HÉTÉROPYRROLES AGISSANT SUR LES RÉCEPTEURS CANNABINOÏDES
  申请人：UNIV CONNECTICUT

  公开号：WO2010104488A1

  公开（公告）日：2010-09-16

  Disclosed are biologically active hetero pyrrole analogs such as imidazoles, thiazoles, oxazoles and pyrazoles capable of interacting with the CB1 and/or CB2 cannabinoid receptors. Aspects disclose hetero pyrrole analogs acting as CB1 and/or CB 1 receptor antagonists, having selectivity for the CB 1 or CB2 receptor, acting as neutral antagonists, acting preferentially on CB 1 receptors located in the peripheral nervous system, and/or acting as nitric oxide donors. Pharmaceutical preparations employing the disclosed analogs and methods of administering therapeutically effective amounts of the disclosed analogs to provide a physiological effect are also disclosed.

  本文披露了生物活性的杂环吡咯类似物，如咪唑、噻唑、噁唑和吡唑，能够与CB1和/或CB2大麻素受体相互作用。本文披露了作为CB1和/或CB 1受体拮抗剂的杂环吡咯类似物，具有对CB 1或CB2受体的选择性，作为中性拮抗剂，首选作用于外周神经系统中的CB 1受体，和/或作为一氧化氮供体的作用。还披露了使用披露的类似物的药物制剂和通过给予治疗有效量的披露的类似物以提供生理效应的方法。
• NOVEL HETEROPYRROLE ANALOGS ACTING ON CANNABINOID RECEPTORS
  申请人：Makriyannis Alexandros

  公开号：US20120046280A1

  公开（公告）日：2012-02-23

  Disclosed are biologically active hetero pyrrole analogs such as imidazoles, thiazoles, oxazoles and pyrazoles capable of interacting with the CB1 and/or CB2 cannabinoid receptors. Aspects disclose hetero pyrrole analogs acting as CB1 and/or CB 1 receptor antagonists, having selectivity for the CB 1 or CB2 receptor, acting as neutral antagonists, acting preferentially on CB 1 receptors located in the peripheral nervous system, and/or acting as nitric oxide donors. Pharmaceutical preparations employing the disclosed analogs and methods of administering therapeutically effective amounts of the disclosed analogs to provide a physiological effect are also disclosed.

  本发明涉及一种生物活性的杂环吡咯类似物，如咪唑、噻唑、噁唑和吡唑，能够与CB1和/或CB2大麻素受体相互作用。其中一些方面揭示了作为CB1和/或CB1受体拮抗剂的杂环吡咯类似物，具有选择性作用于CB1或CB2受体，作为中性拮抗剂，优先作用于位于周围神经系统中的CB1受体，和/或作为一氧化氮供体。还揭示了采用所述类似物的制药制剂和治疗有效量的方法，以提供生理效应。
• Novel Cannabinergic Nitrate Esters and Related Analogs
  申请人：Makriyannis Alexandros

  公开号：US20160096822A1

  公开（公告）日：2016-04-07

  Biologically active cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools or biomarkers. Pharmaceutical compositions may include one or more of the nitrate ester compounds. Medicaments include one or more of the cannabinergic nitrate ester compounds and are useful in treating a variety of diseases. A method of treating, preventing or reducing the severity of a condition includes administering at least one of the disclosed nitrate ester compounds to an individual or animal in need thereof.

  具有生物活性的大麻素硝酸酯及其类似物、制备方法、制药组合物及其作为药物、药理工具或生物标志物的使用方法。制药组合物可以包括一个或多个硝酸酯化合物。药物包括一个或多个大麻素硝酸酯化合物，可用于治疗各种疾病。一种治疗、预防或减轻症状的方法包括向需要的个体或动物中至少给予所披露的硝酸酯化合物之一。
• Cannabinergic nitrate esters and related analogs
  申请人：University of Connecticut

  公开号：US10053444B2

  公开（公告）日：2018-08-21

  Biologically active cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools or biomarkers. Pharmaceutical compositions may include one or more of the nitrate ester compounds. Medicaments include one or more of the cannabinergic nitrate ester compounds and are useful in treating a variety of diseases. A method of treating, preventing or reducing the severity of a condition includes administering at least one of the disclosed nitrate ester compounds to an individual or animal in need thereof.

  具有生物活性的大麻素硝酸酯和相关类似物、制备工艺、药物组合物及其作为药物、药理学工具或生物标记物的使用方法。药物组合物可包括一种或多种硝酸酯化合物。药物包括一种或多种大麻素硝酸酯化合物，可用于治疗多种疾病。一种治疗、预防或减轻病情严重程度的方法包括向有需要的个体或动物施用至少一种所公开的硝酸酯化合物。
• NOVEL HETERO PYRROLE ANALOGS ACTING ON CANNAPINOID RECEPTORS
  申请人：University of Connecticut

  公开号：EP2398323A1

  公开（公告）日：2011-12-28