Icn Pharmaceuticals, Inc.

Dennis A Shuman

Roland K Robins

Kay H Boswell

Rich B Meyer, Jr

Compounds of formula ##STR1## wherein X is --NR.sub.1 R.sub.2, --Cl, --Br or SR; Y is --X, --OH or --NH.sub.2 ; Z is hydrogen or --NH.sub.2 ; and R' is hydrogen or C.sub.1 -C.sub.18 acyl; R being hydrogen, aryl, aralkyl, substituted aryl, substituted aralkyl, or C.sub.1 -C.sub.7 alkyl; and R.sub.1 and R.sub.2 being independently selected from the group consisting of hydrogen, phenyl, C.sub.7 -C.sub.10 aralkyl, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.10 branched chain alkyl, C.sub.1 -C.sub.7 unsaturated alkyl or lower alkyl joined to form a 5 or 6-membered heterocyclic ring, with the proviso that when one of R.sub.1 and R.sub.2 are hydrogen, the other is not. The compounds variously exhibit phosphodiesterase inhibition, protein kinase activation, positive inotropic effects, adenyl cyclase inhibition and other biological activities.

6,8-Disubstituted purine derivatives of 9-.beta.-D-ribofuranosyl

N.sup.6 -Carbamoyl and -carbonyl analogs of adenosine 3',5'-cyclic phosphate (cAMP) are prepared and variously demonstrated to exhibit kinase, adrenal steroidogenisis and lipolysis activation superior to cAMP, inhibit phosphodiesterase, and found to increase cardiac output or, in particular cases, to lower blood pressure.

6-Aminocarbonyl purine 3',5'-cyclic nucleotides

Described herein are novel 6-alkylthio and 6-arylalkylthio purine 3',5' cyclic nucleotides variously exhibiting adenyl cyclase and (in animal studies) tumor inhibitory properties, interferon potentiation, antiviral activity, and the ability to activate adenosine 3',5'-cyclic phosphate-dependent protein kinase while enjoying resistance to phosphodiesterase hydrolysis superior to that of its naturally occuring analog. The compounds are obtained by alkylation of the corresponding 6-thio nucleotide, which is in turn provided by a novel synthetic route.

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Mission Viejo, CA, United States of America

Dennis A Shuman