Discovery of AZD3199, An Inhaled Ultra long Acting beta(2) Receptor Agonist with Rapid Onset of Action

作者：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

来源：ACS Medicinal Chemistry Letters, 2014, 5(4): 416-421.

DOI：10.1021/ml4005232

• uLABA
• beta(2) receptor agonist
• AZD3199
• adrenoreceptor agonist
• asthma
• COPD
• inhaled

A series of dibasic des-hydroxy beta(2) receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human beta-adrenoreceptors demonstrated a series of highly potent and selective beta(2) 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 beta(2) receptor agonist with rapid onset of action.

• 出版日期2014-4