Dove, Stefan and Koch, A. and Franke, R. (1986) Comparative QSAR Studies in a Series of 4-(Imidazol-2'-yl)phenoxypropanolamines and Pyrid-2-yloxypropanolamines with Antihypertensive, Vasodilating and ß-Blocking Properties. Acta Pharmaceutica Jugoslavica 36 (2), pp. 119-128.
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A series of b-blocking, antihypertensive, and vasodilating (2 mechanisms, an unspecific and a b2-agonistic one) 4-(imidazol-2'-yl)-phenoxypropanolamines and pyrid-2-yl-oxopropanolamines (data from J. J. Baldwin et al.) was analyzed by a spectrum of theor. methods: factor anal., Hansch approach, conformational anal., calcn. of at. net charges and of electrostatic potentials. Factor analyses of the biol. data indicate b1- and b2-blockade to be correlated. Antihypertensive action in SH-rats is detd. by b1-antagonism and, addnl., also due to a contribution of b2-agonistic vasodilating activity. In Hansch anal., b1-blockade shows a parabolic dependence on steric and/or hydrophobic parameters of 4'-substituents considering 15 of the imidazole derivs., whereas b2-antagonism is favored by lipophilic and electron-withdrawing groups. The b2-agonistic, vasodilating component highly correlates with at. net charges of the aminic imidazole nitrogen pointing to a H-donor function of the group in the interaction with the b2-receptor. The iminic N can serve as H-acceptor for a 2nd hydrogen bond. Comparisons of the electrostatic potentials of imidazol-25'-yl-Ph and catechol systems indicate a possible bioisosterism of both structures with regard to b-agonistic action. From these results, conclusions are drawn concerning which structural criteria of 4'-substituted 4-(imidazol-2'-yl)phenoxypropanolamines lead to antihypertensively acting symbiotic drugs with b1-blocking and b2-adrenergic properties.
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)|
|Subjects:||500 Science > 570 Life sciences|
500 Science > 540 Chemistry & allied sciences
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||No|
|Owner:||Prof. Dr. Stefan Dove|
|Deposited On:||21 Jan 2009 16:36|
|Last Modified:||05 Aug 2009 13:50|