.beta.1-Selective adrenoceptor antagonists. 2. 4-Ether-linked phenoxypropanolamines

Abstract
A series of 4-substituted phenoxypropanolamines was prepared and examined for .beta.-adrenoceptor activity. Some of the compounds, especially the [4-[2-[[2-(4-fluorophenyl)ethyl]oxy]ethoxy]phenoxy]propanolamines (14, 15 and 24), showed potent .beta.1-blockade with virtually no .beta.2-blockade at doses over 1000 times greater. The compounds also possessed partial agonist activity in rats. Structure-activity relationships are discussed, and conclusions are drawn about the binding sites on .beta.-adrenoceptors. [The use of .beta.-adrenoceptor antagonists is now widely established in the treatment of essential hypertension.].