Heterocyclic analogs of the antihypertensive .beta.-adrenergic blocking agent (S)-2-[3-(tert-butylamino)-2-hydroxypropoxy]-3-cyanopyridine

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Abstract
The syntheses of a series of isoelectronic analogs of (S)-2-[3-(tert-butylamino)-2-hydroxypropoxy]-3-cyanopyridine (1) are described; included in this group are examples of thiazole, isothiazole, thiadiazole, pyrazine and the structurally related naphthyridines. All compounds are similar to 1 in that they contain a cyano group ortho to the aminohydroxypropoxy side chain and meta to the N heteroatom. Several related samples, having additional nuclear substituents and/or groups other than CN in the position adjacent to the aminohydroxypropoxy group, were prepared, and .beta.-adrenoceptor antagonist activity and vasodilating potency were determined. Three compounds, thiazole 2 [(S)-4-[3-(tert-butylamino)-2-hydroxypropoxy]-5-cyanothiazole maleate] and isothiazoles 3 [(S)-3-[3-(tert-butylamino)-2-hydroxypropoxy]-4-cyanoisothiazole maleate] and 27 [(S)-4-bromo-3-[3-(tert-butylamino)-2-hydroxypropoxy]-isothiazole maleate], effectively lowered mean arterial pressure in the SH [spontaneously hypertensive] rat at 5 mg/kg. Compounds 2, 3 and 27 increased iliac blood flow and exhibited .beta.-adrenergic blocking properties in the dog.

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