Document Report Card

ID: ALA1122761

Journal: J Med Chem

Title: Beta 1-selective adrenoceptor antagonists. 3. 4-Azolyl-linked phenoxypropanolamines.

Authors: Machin PJ, Hurst DN, Bradshaw RM, Blaber LC, Burden DT, Melarange RA.

Abstract: 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.

CiteXplore: 6142955

DOI: 10.1021/jm00370a012