AZD3199的发现，一种起效迅速的吸入型超长效β2受体激动剂。
Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action.
作者信息
Stocks Michael J, Alcaraz Lilian, Bailey Andrew, Bonnert Roger, Cadogan Elaine, Christie Jadeen, Dixon John, Connolly Stephen, Cook Anthony, Fisher Adrian, Flaherty Alice, Humphries Alexander, Ingall Anthony, Jordan Stephen, Lawson Mandy, Mullen Alex, Nicholls David, Paine Stuart, Pairaudeau Garry, Young Alan
机构信息
Department of Medicinal Chemistry, Department of Bioscience, and Department of Physical and Metabolic Sciences, AstraZeneca R&D Charnwood , Bakewell Road, Loughborough, Leicestershire LE11 5RH, U.K.
出版信息
ACS Med Chem Lett. 2014 Feb 8;5(4):416-21. doi: 10.1021/ml4005232. eCollection 2014 Apr 10.
A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i.t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultralong acting inhaled β2 receptor agonist with rapid onset of action.
已制备了一系列二元去羟基β2受体激动剂，并对其作为吸入用超长效支气管扩张剂的潜力进行了评估。对人β-肾上腺素能受体活性的测定表明，该系列是一系列高效且选择性的β2受体激动剂，已进入豚鼠组胺诱导的支气管收缩模型进行进一步研究。在通过豚鼠气管环和用乙酰甲胆碱（豚鼠）或卡巴胆碱（人）收缩的人支气管环的起效研究进行进一步评估、气管内（i.t.）给药后在豚鼠中的作用持续时间研究以及进一步的选择性和安全性分析后，AZD3199显示出总体上优异的特性，并作为一种起效迅速的新型超长效吸入β2受体激动剂进入临床评估阶段。
Zotero 插件