N-6 AND 5'-N SUBSTITUTED CARBOXAMIDOADENOSINE DERIVATIVES AS CARDIAC VASODILATORS AND ANTIHYPERTENSIVE AGENTS, AND PROCESS FOR MAKING SAID COMPOUNDS

摘要

Compounds of formula (I), wherein R1 represents secondary alkyl; aralkyl; cycloalkyl; heteroaryl substituted alkyl; norbornyl; and substituted secondary alkyl, aralkyl, cycloalkyl, heteroaryl substituted alkyl, norbornyl; and para-substituted phenyl groups; and R2 and R3 are hydrogen or pharmacologically acceptable acyl groups. The compounds of the invention are useful as cardiovascular vasodilator or anti-hypertensive agents. The therapeutically useful compounds of the invention as well as similar 5'-N and N-6 substituted adenosine 5'-uronamides are prepared, in accordance with a novel process, from isopropylidene (or otherwise suitably blocked) inosine-5'-uronic acid. Isopropylideneinosine-5'-uronic acid is reacted with a suitable inorganic acid halide, such as thionyl chloride, to yield 6-halogeno-9-¨AD2',3'-O-isopropylidene-$(1,3)$-D-ribofuranosyl-5-uronic acid halide¨BD-9H-purine. This intermediate is reacted with an amine of the general formula R4, R5NH to give a 6-halogeno substituted, substituted uronic acid amide of formula (II), wherein X is halogen. Reaction of the latter intermediate with an amine of the formula R1-NH2, and removal of the isopropylidene (or other) blocking groups yields the compounds of the invention.