کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10588253 981450 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The discovery of long-acting saligenin β2 adrenergic receptor agonists incorporating hydantoin or uracil rings
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
The discovery of long-acting saligenin β2 adrenergic receptor agonists incorporating hydantoin or uracil rings
چکیده انگلیسی
A series of novel, potent and selective human β2 adrenoceptor agonists incorporating a hydantoin or a uracil ring on the right-hand side phenyl ring of (R)-salmeterol is presented. Hydantoin 12a had long duration of action in vitro on guinea pig trachea, and 12 h in guinea pigs in vivo at its EC90 25 μM. It had lower oral absorption than salmeterol in rats, and lower bioavailability than salmeterol in vivo in both rats and dogs (2% and 5%, respectively). An improved method for measuring the absorbed fraction of analogues dosed to rats, which considers the glucuronidated fraction is presented. Compound 12a was metabolised in human liver microsomes and hepatocytes to the active hydantoic acid 12m.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 14, 15 July 2011, Pages 4192-4201
نویسندگان
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