US 5,310,731 A · N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardiac vasodilators and antihypertensive agents

Abstract

Compounds of the formula ##STR1## are disclosed, wherein R.sub.1, 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 R.sub.2 and R.sub.3 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-[ 2',3' -O-isopropylidene-.beta.-D-ribofuranosyl-5-uronic acid halide] -9H-purine. This intermediate is reacted with an amine of the general formula R.sub.4,R.sub.5 NH to give a 6-halogeno substituted, substituted uronic acid amide of the formula ##STR2## wherein X is halogen. Reaction of the latter intermediate with an amine of the formula R.sub.1 --NH.sub.2, and removal of the isopropylidene (or other) blocking groups yields the compounds of the invention.

Claims35

Dependent claims

Compounds of the formula:

##STR9## wherein:
R.sub.1 represents secondary alkyl having from 3 to 10 carbons, phenylalkyl, having from 1 to 7 carbons in the alkyl chain;
mono- to penta-alkoxy phenylalkyl wherein said alkoxy contains from 1 to 3 carbons and said alkyl contains from 1 to 7 carbons;
monohalophenylalkyl wherein said alkyl contains from 1 to 4 carbons;
cycloalkyl wherein the ring contains from 3 to 8 carbons;
bicycloalkyl wherein the rings together contain from 7 to 10 carbons;
thienylalkyl wherein said alkyl contains from one to four carbons;
pyridylalkyl wherein said alkyl contains from one to four carbons;
R.sub.2 and R.sub.3 are hydrogen;
R.sub.4 is alkyl having 1 to 7 carbon atoms;
or hydroxyalkyl which contains from 1 to 4 carbons;
or secondary alkyl which contains from 3-8 carbons;
or allylic alkenyl which contains from 3 to 7 carbons;
or cycloalkyl wherein the ring contains from 3 to 7 carbons;
or phenylalkyl wherein said alkyl contains from 1 to 4 carbons;
or monoalkoxy phenylalkyl wherein said alkoxy and said alkyl each contain from 1 to 4 carbons;
or thienylalkyl wherein said alkyl contains from 1 to 4 carbons;
and R.sub.5 is hydrogen, or straight chain lower alkyl having 1 to 4 carbons.

15 more elements

Dependencies are inferred from the claim text.

N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardiac vasodilators and antihypertensive agents

Life of this patent

N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardiac vasodilators and antihypertensive agents

Life of this patent

Abstract

Claims35