5-fluoro- and 8-fluorotrimetoquinol: selective beta 2-adrenoceptor agonists.
The 5-fluoro and 8-fluoro analogues of trimetoquinol, TMQ, have been synthesized and evaluated for beta 2- and beta 1-adrenoceptor activity in guinea pig trachea and atria, respectively. The fluoro analogues of TMQ maintained potent beta 2-adrenoceptor agonist activity but had reduced beta 1-adrenoceptor agonist activity. The changes in beta 1-activity of these compounds were correlated to differences in phenolic pKa's. The beta 1- and beta 2-adrenoceptor actions of 2 and 3 were blocked in a competitive manner by propranolol. The enhanced beta 2/beta 1 selectivity for the analogues was found to be 8-fluoro analogue 3 greater than 5-fluoro analogue 2 greater than trimetoquinol (1).
D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D016275:Atrial Function; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014132:Trachea / Q000502:physiology; D014213:Tretoquinol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D007202:Indicators and Reagents; D007546:Isoquinolines; D011943:Receptors, Adrenergic, beta; C050943:5-fluorotrimetoquinol; C050944:8-fluorotrimetoquinol; D011433:Propranolol; D014213:Tretoquinol