Syntex (u.s.a.) Inc.

Syntex LLC

Julien P Verheyden

John C Martin

Ernest J Prisbe

Daniel P McGee

Hans Maag

G V Madhaven

G V Madhavan

Nucleoside compounds of the formula ##STR1## wherein: B is a purine or a pyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH.sub.3 or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is ##STR2## where n is zero, one, two or three; and Z' is N.sub.3 or OCH.sub.3 ; provided that when X' and Y' are OH and Z' is N.sub.3, B is not cytosine, and when X' and Y' are OH and Z' is OCH.sub.3, B is not uracil, adenine or cytosine; and the pharmaceutically acceptable esters, ethers and salts thereof, have been found to have potent antiviral activity with a high therapeutic ratio.

Antiviral agents

Compounds useful as antiviral agents are defined by the following formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is hydrogen or --C(O)R.sup.7 wherein R.sup.7 is hydrogen, alkyl of one to nineteen carbon atoms, hydroxyalkyl of one to eight carbon atoms, alkoxyalkyl of two to nine carbon atoms, alkenyl of two to nineteen carbon atoms, phenyl, 1-adamantyl or 2-carboxyethyl and the pharmaceutically acceptable alkali metal salts thereof;

Substituted 9-(1 or 3-monoacyloxy or 1,3-diacyloxy-2-propoxymethyl)

Compounds useful as antiviral agents are defined by the following formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein

Process for preparing guanine derivatives

Compounds useful as antiviral agents are depicted in the formula: ##STR1## wherein: X is oxygen or NH, Y is hydrogen, iodo, fluoro, methyl or trifluoromethyl, Z is hydrogen or fluoro and Z' is fluoro; and the wavy line indicates that the group may be above or below the plane of the ring; and the pharmaceutically acceptable acid addition salts thereof.

Tricyclic derivatives of substituted pyrimidines

Process and novel intermediates for preparing 9-(1,3-dihydroxy-2-propoxymethyl)guanine and 2,6-diamino-9-(1,3-dihydroxy-2-propoxymethyl)purine and certain esters thereof. The present process and intermediates reduce the number of reaction steps to prepare these compounds as compared to prior processes. The products are useful as antiviral agents.

Process for preparing

Compounds useful as antiviral agents are defined by the following formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 and R.sup.2 are both --C(O)R.sup.7 wherein R.sup.7 is 1-adamantyl;

Compounds useful as antiviral agents are defined by the following formula: ##STR1## wherein R.sup.1 is hydrogen, --C(Y)OR.sup.7 or --C(O)NHR.sup.7 wherein R.sup.7 is alkyl of one to twelve carbon atoms, alkenyl of two to twelve carbon atoms, cyclopentyl, cyclohexyl, phenyl or benzyl;

Substituted 9-(1-O- or 3-O-monosubstituted or 1,3-di-O-substituted

Novel 4-substituted-5-hydroxymethyl-1,2-cyclopentanediols or 1-cyclopentanol substituted at the 3-position by various heterocyclic groups are useful as antiviral agents.

Purinyl or pyrimidinyl substituted hydroxycyclopentane compounds useful

The compounds 9-(1,3-dihydroxy-2-propoxymethyl)guanine and the pharmaceutically acceptable salts thereof are useful as antiviral agents. The compound 1,3-dibenzyloxy-2-acetyloxy-methoxypropane is useful as an intermediate for the preparation of 9-(1,3-dihydroxy-2-propoxymethyl)guanine.

1,3-dibenzyloxy-2-acetoxymethoxypropane, intermediate for

1-Monophosphate esters, 1,3-bisphosphate esters and cyclic phosphate esters of 9-(1,3-dihydroxy-2-propoxymethyl)guanine are useful as antiviral agents.

Substituted 9-(1-0- or 3-0-monosubstituted or 1,3-Di-0-substituted

The compound 9-(1,3-dihydroxy-2-propoxymethyl)guanine and the pharmaceutically acceptable salts thereof are useful as antiviral agents.

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Los Altos, CA, United States of America

Julien P Verheyden