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

Abstract

The synthesis of a series of (E)-1-amino-3-[2-(2-isoxazolylethenyl)phenoxyl-2-propanols is described. These compounds were found to 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. 3a 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. However, in general, those compounds having the most potent beta-adrenoceptor blocking activity also lowered blood pressure most effectively.

Synthesis of Spiro- and Fused Heterocycles via (4+4) Annulation of Sulfonylphthalide with o-Hydroxystyrenyl Derivatives

“…Spiro-lactones 7b and 7c were formed in better yields (73% each) when isoxazoles 5b and 5c , bearing weakly electron-withdrawing substituents such as bromine and chlorine on the aryl ring, were employed as substrates. 2-Hydroxynaphthyl-derived isoxazole 5d , as observed in the previous case, is not a compatible substrate for this transformation, presumably for steric reasons …”

“…The structure was solved by direct method Shelxs97 and refined by full-matrix least-squares against F 2 using Shelxl97 software. Sulfonylphthalide 1 , o -hydroxychalcone 2 , o -hydroxynitrostyrylisoxazole 5 , and o -hydroxystyrylisoxazole without a nitro group were prepared by literature methods. The identity and purity of substrates 1 , 2 , and 5 were in general confirmed by comparison of their physical and spectroscopic data with those reported in the literature.…”