Hypertensive effects and structure-activity relationships of 5-omega-aminoalkyl isoxazoles.
Structure-activity and dose-response relationships of a series of novel 5-omega aminoalkyl and 5-omega-amino-heteroalkyl isoxazoles on blood pressure and heart rate of Sprague-Dawley rats have been investigated. To differentiate between peripheral and central cardiovascular actions of those compounds a pithed rat and anaesthetized rat preparation was used. Most of the compounds investigated exhibit potent hypertensive actions. The hypertensive effects of the tested compounds is depending on the amphiphilic character of the isoxazoles represented by a basic moiety in a definite distance to the phenyl substituents. To achieve high pharmacological activity a fully flexible side chain is requested, too. Possible mechanisms of action are discussed.
Dannhardt
G
G
Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt/Main Fed. Rep. of Germany.
Dominiak
P
P
Laufer
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D007555:Isoxazoles