Increased inhibitory action against adenosine 5'-triphosphate in the isolated taenia of the guinea-pig caecum by substitution in the A-ring of 2-phenylisatogen.
1 The ability of a series of 17 isatogen derivatives to relax smooth muscle, inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in isolated mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 Substitution in the 4- and 7-positions of the A-ring gave compounds that were strong inhibitors of mitochondrial ATP synthesis and potent, non-specific smooth muscle relaxants. The compounds also possessed ATP-receptor blocking activity. 3 Substitution in the 5- and 6-positions of the A-ring decreased both the relaxant effect on smooth muscle and inhibition of ATP synthesis, whilst enhancing ATP-receptor antagonism. 4 In a series of 6-substituted 2-phenylisatogens, 6-methoxy-2-phenylisatogen was the most effective ATP-receptor antagonist. This compound also showed the greatest separation of the desired pharmacological activity (ATP-receptor blockade) from the other two activities (smooth muscle relaxation and inhibition of mitochondrial ATP synthesis).
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000818:Animals; D002432:Cecum / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D008931:Mitochondria, Muscle / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013329:Structure-Activity Relationship
D007211:Indoles; C008858:2-phenylisatogen; D007510:Isatin; D000255:Adenosine Triphosphate