1-(2-methylphenoxy)propan-2-amine hydrochloride | 89763-84-8

• 英文名称: 1-(2-methylphenoxy)propan-2-amine hydrochloride
• 英文别名: 1-(o-Tolyloxy)propan-2-amine hydrochloride；1-(2-methylphenoxy)propan-2-amine;hydrochloride
• CAS: 89763-84-8
• 化学式: C₁₀H₁₅NO*ClH
• 分子量: 201.696
• InChiKey: QIJGZAUWGRQVAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.14
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  邻甲酚 在 盐酸 、 palladium 10% on activated carbon 、 氨 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 6.0h， 生成 1-(2-methylphenoxy)propan-2-amine hydrochloride
  参考文献：
  名称：

  Pharmacological profiling of JME-173, a novel mexiletine derivative combining dual anti-inflammatory/anti-spasmodic functions and limited action in Na+ channels

  摘要：

  Existing evidence suggests that the local anaesthetic mexiletine can be beneficial for patients with asthma. However, caution is required since anaesthesia of the airways inhibits protective bronchodilator neuronal reflexes, limiting applications in conditions of hyperirritable airways. Here, we describe the synthesis of a new series of mexiletine analogues, which were screened for reduced activity in Na+ channels and improved smooth muscle relaxant effects, that were evaluated using the patch-clamp technique and an isolated tracheal organ bath, respectively. JME-173 (1-(4-bromo-3,5-dimethylphenoxy)propan-2-amine) was the most effective among the four mexiletine analogues investigated. JME-173 was then studied in vivo using a murine model of lung inflammation induced by cigarette smoke (CS) and in vitro using neutrophil chemotaxis and mast cell degranulation assays. Finally, the JME-173 pharmacokinetic profile was assessed using HPLC-MS/MS bioanalytical method. JME-173 directly inhibited IL-8 (CXCL8)- and FMLP-induced human neutrophil chemotaxis and allergen-induced mast cell degranulation. After oral administration 1 h before CS exposure, JME-173 (50 mg/kg) strongly reduced the increased number of macrophages and neutrophils recovered in the bronchoalveolar effluent without altering lymphocyte counts. Pharmacokinetic experiments of JME-173 (10 mg/kg, orally) showed values of maximum concentration (C-max), maximum time (T-max), area under the blood concentration-time curve (AUC(0-t)) and area under the blood concentration-time curve from 0-Inf (AUC(0-inf)) of 163.3 + 38.3 ng/mL, 1.2 +/- 0.3 h, 729.4 +/- 118.3 ng*h/ml and 868.9 + 117.1 ng*h/ml (means + S.E.M.), respectively. Collectively, these findings suggest that JME-173 has the potential to be an effective oral treatment for diseases associated with bronchoconstriction and inflammation.

  DOI：

  10.1016/j.ejphar.2020.173367

文献信息

• Antiarrhythmic Hit to Lead Refinement in a Dish Using Patient-Derived iPSC Cardiomyocytes
  作者：John R. Cashman、Daniel Ryan、Wesley L. McKeithan、Karl Okolotowicz、Jorge Gomez-Galeno、Mark Johnson、Kevin J. Sampson、Robert S. Kass、Arash Pezhouman、Hrayr S. Karagueuzian、Mark Mercola

  DOI：10.1021/acs.jmedchem.0c01545

  日期：2021.5.13
• ANTI-VIRAL COMPOUNDS
  申请人：ABBOTT LABORATORIES

  公开号：EP1979348A2

  公开（公告）日：2008-10-15
• [EN] ANTI-VIRAL COMPOUNDS<br/>[FR] COMPOSES ANTIVIRAUX
  申请人：ABBOTT LAB

  公开号：WO2007076034A2

  公开（公告）日：2007-07-05

  [EN] Compounds effective in inhibiting replication of Hepatitis C virus ("HCV") or other viruses are disclosed. This invention is also directed to compositions comprising such compounds, co-formulation or co-administration of such compounds with other anti-viral or therapeutic agents, processes and intermediates for the syntheses of such compounds, and methods of using such compounds for the treatment of HCV or other viral infections.
  [FR] L'invention porte sur des composés efficaces pour inhiber la réplication du virus de l'hépatite C (VHC) ou d'autres virus. L'invention concerne également des compositions renfermant lesdits composés, la co-formulation ou la co-administration desdits composés avec d'autres agents anti-viraux ou thérapeutiques, des procédés et des intermédiaires destinés à la synthèse desdits composés, et des procédés d'utilisation desdits composés pour le traitement du VHC.