Beta 1-selective adrenoceptor antagonists. 3. 4-Azolyl-linked phenoxypropanolamines.
A series of 4-substituted phenoxypropanolamines has been prepared and examined for beta-adrenoceptor activity. The 4-substituents, di- and triazole ring systems connected to the phenoxy ring by different length chains, were chosen as a means of introducing cardioselectivity. This has been achieved, especially in the 1-[4-[(4-chloropyrazol-1-yl)methoxy] phenoxy]-3-(isopropylamino)-2-propanol (11), the 4-[(2H-1,2,3-triazol-2-yl)methoxy] analogue (21), and the 4-[2-(2H-1,2,3-triazol-2-yl)ethoxy] analogue (22), which show potent beta 1-blockade with selectivity ratios in excess of 100:1. Structure-activity relationships are discussed, and the optimum position of the heteroatom in the 4-substituent is defined.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007202:Indicators and Reagents; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D007202:Indicators and Reagents; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014230:Triazoles