1,2-ジヒドロ-5-(イミダゾ[1,2-a]ピリジン-6-イル)-6-メチル-2-オキソ-3-ピリジンカルボニトリル·塩酸塩

説明Coatec was launched in Japan for acute cardiac insufficiency in cases resistant to other treatments. There are three related synthetic routes, 5-6 steps each, to loprinone all converging on 1-(imidazo[1,2a]pyridyl-6-yl)-Zpropanone as an advanced intermediate. It is a potent and selective inhibitor of PDE Ⅲ and a long lasting, orally active, positive inotropic agent. The PDE Ⅲ inhibition caused increased levels of CAMP which leads to the positive inotropic effect that was not altered by β or H2-preceptor antagonists. It was 100 times less potent at PDE I and PDE Ⅱ with no Na-K-ATPase activity. Improved hemodynamic parameters with slight changes in heart rate and blood pressure were seen in vivo. It is not mutagenic and its primary metabolite was less active.