N-{2-[4-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-5-methyl-2-(2H-1,2,3-triazol-2-yl)benzamide | 1381970-61-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-{2-[4-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-5-methyl-2-(2H-1,2,3-triazol-2-yl)benzamide
• 英文别名: N-[2-[4-(5-fluoropyridin-2-yl)pyrazol-1-yl]ethyl]-5-methyl-2-(triazol-2-yl)benzamide
• CAS: 1381970-61-1
• 化学式: C₂₀H₁₈FN₇O
• 分子量: 391.408
• InChiKey: IIOKTGYGYMXVDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  90.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-碘代丙烷 、 N-{2-[4-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-5-methyl-2-(2H-1,2,3-triazol-2-yl)benzamide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.0h， 以12%的产率得到N-{2-[4-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-5-methyl-N-(propan-2-yl)-2-(2H-1,2,3-triazol-2-yl)benzamide
  参考文献：
  名称：

  Discovery and in vitro and in vivo profiles of N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide as a novel class of dual orexin receptor antagonist

  摘要：

  Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3 mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4 h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.044
• 作为产物：
  描述：

  2-溴-5-氟吡啶 在 盐酸 、 四(三苯基膦)钯 、 N-[(dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide 、 sodium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 29.0h， 生成 N-{2-[4-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-5-methyl-2-(2H-1,2,3-triazol-2-yl)benzamide
  参考文献：
  名称：

  Discovery and in vitro and in vivo profiles of N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide as a novel class of dual orexin receptor antagonist

  摘要：

  Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3 mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4 h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.044

文献信息

• PYRAZOLE DERIVATIVE
  申请人：Nozawa Dai

  公开号：US20130281465A1

  公开（公告）日：2013-10-24

  A compound represented by formula (IA) or a pharmaceutically acceptable salt thereof, which is useful for the treatment or prevention of diseases such sleep disorder, depression, anxiety disorder, panic disorder, schizophrenia, drug dependence, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, pain, gastrointestinal diseases, epilepsy, inflammation, immune-related diseases, endocrine-related diseases, and hypertension, and of which the action relies on an orexin (OX) receptor antagonistic activity.

  一种由化学式（IA）表示的化合物或其药用可接受的盐，用于治疗或预防睡眠障碍、抑郁症、焦虑症、恐慌症、精神分裂症、药物依赖、阿尔茨海默病、帕金森病、亨廷顿舞蹈症、进食障碍、疼痛、胃肠疾病、癫痫、炎症、免疫相关疾病、内分泌相关疾病和高血压等疾病的治疗，其作用依赖于促脑皮质醒脑素（OX）受体拮抗活性。
• Identification of highly selective and potent orexin receptor 1 antagonists derived from a dual orexin receptor 1/2 antagonist based on the structural framework of pyrazoylethylbenzamide
  作者：Aya Futamura、Dai Nozawa、Yuko Araki、Yunoshin Tamura、Seiken Tokura、Hiroshi Kawamoto、Yuichi Tokumaru、Sora Kakihara、Takeshi Aoki、Norikazu Ohtake

  DOI：10.1016/j.bmc.2017.07.051

  日期：2017.10

  novel class of pyrazolylethylbenzamide orexin receptor 1-selective antagonists are described. Further derivatization of the prototype dual orexin receptor 1/2 antagonist lead (1) by installing a (S)-methyl group into the ethyl linker moiety between the pyrazole ring and benzamide resulted in an increase of the antagonist potency against orexin receptor 1/2 receptors. Optimization of the benzamide and pyrazole

  描述了新型吡唑基乙基苯甲酰胺orexin受体1-选择性拮抗剂的设计，合成和结构活性关系。通过在吡唑环和苯甲酰胺之间的乙基连接基团中安装一个（S）-甲基进一步使原型双orexin受体1/2拮抗剂前导物（1）进一步衍生，从而提高了对抗orexin受体1/2的拮抗剂效价受体。化合物2和9b的苯甲酰胺和吡唑部分的优化导致鉴定N-乙基-5-氟-N -（2 S）-1- [5-（4-氟苯基）-2 H-四唑-2-基]丙-2-基} -2-（嘧啶-2-基）苯甲酰胺（24），其对食欲素受体1表现出优异的拮抗活性，IC 50为2.01 nM，选择性为265倍对于orexin受体1而言，它比orexin受体2更重要。
• [EN] PYRAZOLE DERIVATIVE<br/>[FR] DÉRIVÉ DE PYRAZOLE
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2012081692A1

  公开（公告）日：2012-06-21

  　式（ＩＡ）で示される化合物又はその医薬上許容される塩は、オレキシン（ＯＸ）受容体拮抗作用に基づいた、睡眠障害、うつ病、不安障害、パニック障害、統合失調症、薬物依存症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害、疼痛、消化器疾患、てんかん、炎症、免疫関連疾患、内分泌関連疾患、高血圧等の疾患の治療又は予防に有用である。

  化合物或其医药上允许的盐，如式（IA）所示，基于促进睡眠障碍、抑郁症、焦虑症、惊恐障碍、精神分裂症、药物成瘾、阿尔茨海默病、帕金森病、亨廷顿舞蹈病、进食障碍、疼痛、消化系统疾病、癫痫、炎症、免疫相关疾病、内分泌相关疾病、高血压等疾病的治疗或预防，具有促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进促进的作用。