Synthesis of imidazo[1,2-a]pyrazine derivatives with uterine-relaxing, antibronchospastic, and cardiac-stimulating properties.
A series of imidazo[1,2-alpha]pyrazine derivatives was synthesized by condensation of alpha-halogenocarbonyl compounds and aminopyrazines. Various compounds resulted from competitive reactions or reagent isomerization and demonstrated in vitro uterine-relaxing and in vivo antibronchospastic activities. On isolated atria, 5-bromoimidazo-[1,2-alpha]pyrazine showed positive chronotropic and inotropic properties; the latter was associated with an increase in the cyclic AMP tissue concentration. Potentiation of the isoproterenol positive inotropic effect of 5-bromoimidazo[1,2-alpha]pyrazine and the lack of blockade of the 5-bromoimidazo[1,2-alpha]pyrazine positive inotropic effect by propranolol suggested phosphodiesterase-inhibiting properties.
D000818:Animals; D016275:Atrial Function; D001986:Bronchial Spasm / Q000188:drug therapy*; D055598:Chemical Phenomena; D002621:Chemistry; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects*
D007093:Imidazoles; D011719:Pyrazines; C040374:5-bromoimidazo(1,2-a)pyrazine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol