Whitby Research, Inc.

Robert D Thompson

Ray A Olsson

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.

N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardiac

The present invention discloses a compound of the formula: ##STR1## where R.sub.1 is hydrogen or the group ##STR2## where R.sub.3 and R.sub.4 are the same or different and are hydrogen, C.sub.1 to C.sub.12 linear or branched alkyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.6 to C.sub.10 aryl unsubstituted or substituted with C.sub.1 to C.sub.6 linear or branched alkyl, C.sub.1 to C.sub.6 linear or branched alkoxy, nitro, amino, amino substituted with at least one C.sub.1 to C.sub.6 linear or branched alkyl or phenyl, C.sub.2 to C.sub.10 aralkyl, C.sub.4 to C.sub.8 heteroaryl wherein said heteroatom is nitrogen, phosphorous, sulfur or oxygen, and R.sub.2 is hydrogen, or taken together with R.sub.5, forms a chemical bond, and R is a monosaccharide radical selected from the group consisting essentially of glucose, fructose, ribose, 2-deoxyribose, mannose, galactose, xylose and arabinose.

2-hydrazoadenosines and their utility for the treatmeat of vascular

Compounds are disclosed having the formulae: ##STR1## wherein R.sub.1 is selected from the group, consisting of radicals represented by the general formulae: ##STR2## wherein Y is selected from the group consisting of lower alkyl, lower alkoxy, and halogen; Z is oxygen, sulfur or --NH, Q is --CH or nitrogen; a is zero or an integer of from one to three; and

2-aralkoxy and 2-alkoxy adenosine derivatives as coronary vasodilators

New, N-6 monosubstituted adenosine derivatives are disclosed which have significant cardiac vasodilatory effect. The compounds of the invention include 6-(cyclo-butyl amino)-9-(.beta.-D-ribofuranosyl)-9H-purine, 6-(2-methyl-2-phenyl hydrazino)-9-(.beta.-D-ribofuranosyl)-9H-purine, and compounds of the general formula: ##STR1## wherein R.sub.1 is H, lower alkyl, lower alkoxy, alkylamino, or arylamino, R.sub.2 is H, lower alkyl, hydroxymethyl, phenyl or substituted phenyl, R.sub.3 is H, lower alkyl, phenyl, substituted phenyl, R.sub.3 is H, lower alkyl, phenyl, substituted phenyl, 2 or 3-thienyl, or 2 or 3-pyridyl, R.sub.4 is H or lower alkyl, and R.sub.5 is H or lower acyl. Particularly active as a cardiac vasodilator is the compound (-)-6-(R-1-phenyl-2-butyl amino)-9-(.beta.-D-ribofuranosyl)-9H-purine.

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Tampa, FL, United States of America

Robert D Thompson