Heterocyclic analogues of the antihypertensive beta-adrenergic blocking agent (S)-2-[3-(ter-butylamino)-2-hydroxypropoxy]-3-cyanopyridine.
The synthesis of a series of isoelectronic analogues 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 of the compounds are similar to 1 in that they contain a cyano group ortho to the aminohydroxypropoxy side chain and meta to the nitrogen heteroatom. In addition, several related examples, 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 and isothiazoles 3 and 27, effectively lowered mean arterial pressure in the SH rat at 5 mg/kg. Compounds 2, 3, and 27 increased iliac blood flow and exhibited beta-adrenergic blocking properties in the dog.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D011725:Pyridines; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011725:Pyridines; D014665:Vasodilator Agents; D007545:Isoproterenol