Studies on the Synthesis of Compounds Related to Adenosine 3', 5'-Cyclic Phosphate. V. : Synthesis and Cardiac Effect of N⁶-Alkyladenosine 3', 5'-Cyclic Phosphates and Their 8-Benzylthio Derivatives

Abstract

A series of N⁶-alkyladenosine 3', 5'-cyclic phosphates (N⁶-alkyl cAMPs) (3) and N⁶-alkyl-8-benzylthio cAMPs (4) was synthesized from cAMP (1) and 8-benzylthio cAMP (2) by means of a one-pot reaction. This reaction proceeded by reductive alkylation in acetic acid with aldehydes and sodium cyanoborohydride. These cAMP derivatives were evaluated for inotropic and chronotropic effects on the isolated guinea pig papillary muscle and right atria. Several N⁶-alkyl cAMPs (3) were surprisingly more active than compounds 4 in these actions. Among them, N⁶-hexyl cAMP (3f) and M⁶-heptyl cAMP (3g) showed strongly positive inotropic effects (PIE) and moderately negative chronotropic effects.