US RE37,045 E1 · N-6 substituted-5′-(N-substituted carboxamide)adenosines as cardiac vasodilator and antihypertensive agents

Abstract

Compounds of the formula are disclosed, 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-[2′,3′-O-isopropylidene-β-D-ribofuranosyl-5-uronic acid halide]-9H-purine. This intermediate is reacted with an amine of the general formula R4R5NH to give a 6-halogeno substituted, substituted uronic acid amide of the formula 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.

Claims35

Dependent claims

Compounds A compound of the formula:

wherein:
R1 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;
R2 and R3 are hydrogen;
R4 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 R5 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-substituted carboxamide)adenosines as cardiac vasodilator and antihypertensive agents

Life of this patent

N-6 substituted-5′-(N-substituted carboxamide)adenosines as cardiac vasodilator and antihypertensive agents

Life of this patent

Abstract

Claims35