2-(Isoxazolylethenyl)phenoxypropanolamines: a new class of .beta.-receptor antagonists with antihypertensive activity

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Abstract
The synthesis of a series of (E)-1-amino-3-[2-(2-isoxazolylethenyl)phenoxy]-2-propanols is described. These compounds have .beta.- and .alpha.-adrenergic blocking properties, as well as hypotensive and antihypertensive properties. The .beta.-adrenoceptor antagonism of all these compounds was more pronounced than their .alpha.-sympatholytic and hypotensive activity, (E)-[(1,1-dimethylethyl)amino]-3-[2-[2-(3-methyl-5-isoxazolyl)ethenyl]phenoxy]-2-propanolol was 16 times more potent than labetalol in .beta.-adrenergic receptor blockade and was effective in lowering blood pressure in acute trials on spontaneously hypertensive rats at a dosage of 15 mg/kg. Structure-activity considerations showed that antihypertensive potency was more sensitive to structural variations than .beta.-adrenoceptor antagonistic activity. Those compounds having the most potent .beta.-adrenoceptor blocking activity also lowered blood pressure most effectively.