1,1-dimethylethyl 4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinecarboxylate | 1119798-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,1-dimethylethyl 4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinecarboxylate
• 英文别名: tert-butyl 4-(6-butylquinolin-8-yl)oxypiperidine-1-carboxylate
• CAS: 1119798-85-4
• 化学式: C₂₃H₃₂N₂O₃
• 分子量: 384.519
• InChiKey: FHYOHCRHMIKPDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinecarboxylate 在 盐酸 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 丁酮 为溶剂， 反应 26.0h， 生成 N-(4-{4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinyl}butyl)ethanesulfonamide
  参考文献：
  名称：

  Identification of selective 8-(piperidin-4-yloxy)quinoline sulfone and sulfonamide histamine H1 receptor antagonists for use in allergic rhinitis

  摘要：

  A series of potent, selective and long-acting quinoline-based sulfonamide human H-1 histamine receptor antagonists, designed for once-daily intranasal administration for the treatment of rhinitis were developed. Sulfonamide 33b had a slightly lower affinity for the H-1 receptor than azelastine, had low oral bioavailability in the rat and dog, and was turned over to five major metabolites. Furthermore, 33b had longer duration of action than azelastine in guinea pigs, lower rat brain-penetration, and did not cause time dependent inhibition of CYP2D6 or CYP3A4. The clinical dose in humans is expected to be low (approximately 0.5 mg per day) based on the clinical dose used for azelastine and a comparison of efficacy data from animal models for 33b and azelastine. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2017.09.020
• 作为产物：
  描述：

  6-溴-8-氟喹啉 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 1.5h， 生成 1,1-dimethylethyl 4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinecarboxylate
  参考文献：
  名称：

  Identification of selective 8-(piperidin-4-yloxy)quinoline sulfone and sulfonamide histamine H1 receptor antagonists for use in allergic rhinitis

  摘要：

  A series of potent, selective and long-acting quinoline-based sulfonamide human H-1 histamine receptor antagonists, designed for once-daily intranasal administration for the treatment of rhinitis were developed. Sulfonamide 33b had a slightly lower affinity for the H-1 receptor than azelastine, had low oral bioavailability in the rat and dog, and was turned over to five major metabolites. Furthermore, 33b had longer duration of action than azelastine in guinea pigs, lower rat brain-penetration, and did not cause time dependent inhibition of CYP2D6 or CYP3A4. The clinical dose in humans is expected to be low (approximately 0.5 mg per day) based on the clinical dose used for azelastine and a comparison of efficacy data from animal models for 33b and azelastine. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2017.09.020

文献信息

• [EN] QUINOLINE DERIVATIVES AND THEIR USES FOR RHINITIS AND URTICARIA<br/>[FR] DÉRIVÉS DE QUINOLINE ET APPLICATIONS ASSOCIÉES DANS LA RHINITE ET L'URTICAIRE
  申请人：GLAXO GROUP LTD

  公开号：WO2010094643A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及式(I)的化合物及其盐，其制备方法，含有它们的组合物，以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• Compounds
  申请人：Gore Paul Martin

  公开号：US20090270355A1

  公开（公告）日：2009-10-29

  The present invention relates to a compound which is N-(4-4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinyl}butyl)ethanesulfonamide and salts thereof, processes for its preparation, to compositions containing it and to its use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及一种化合物，即N-(4-4-[(6-丁基-8-喹啉基)氧基]-1-哌啶基}丁基)乙烷磺酰胺及其盐，以及其制备方法、含有该化合物的组合物，以及在治疗各种疾病（如过敏性鼻炎）中的用途。
• [EN] QUINOLINE DERIVATIVES USED TO TREAT INFLAMMATORY AND ALLERGIC DISEASES<br/>[FR] DÉRIVÉS DE QUINOLÉINE UTILISÉS POUR TRAITER DES MALADIES INFLAMMATOIRES ET ALLERGIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2009050204A1

  公开（公告）日：2009-04-23

  The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及式(I)的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的应用。
• SUBSTITUTED QUINOLINE DERIVATIVES AS H1 RECEPTOR ANTAGONISTS
  申请人：Gore Paul Martin

  公开号：US20110281909A1

  公开（公告）日：2011-11-17

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及公式（I）的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的应用。
• QUINOLINE DERIVATIVES USED TO TREAT INFLAMMATORY AND ALLERGIC DISEASES
  申请人：Gore Paul Martin

  公开号：US20100222349A1

  公开（公告）日：2010-09-02

  The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及式(I)的化合物及其盐，其制备过程，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的应用。