Merck + Co., Inc.

John D Karkas

Richard L Tolman

Wallace T Ashton

Malcolm MacCoss

Derek J Von Langen

Arthur K Field

Certain prodrugs such as ##STR1## are useful in the inhibition of herpes virus thymidine kinase, the prevention or treatment of recurrent infection by herpes virus, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing or treating recurrent infection by herpes virus are also described.

Prodrugs of herpes TK inhibitors

9-(1,3-Dihydroxy-2-propoxymethyl)guanine and 9-(2,3-dihydroxy-1-propoxymethyl)guanine have been found to have potent anti-viral activity against herpes viruses. These compounds, their acyl derivatives, their phosphate derivatives and their pharmaceutically acceptable salts, pharmaceutical formulations containing these compounds, the treatment of DNA viral or herpes viral infections with these compounds, method of preparing these compounds, and novel intermediates useful in their preparation are all disclosed. The compounds may be prepared by reaction of the appropriate acetoxymethyl ether with diacetylguanine, followed by deprotection. The acetoxymethyl ethers may be obtained by reaction of glycerol formal with acetic anhydride in the presence of a catalyst.

Anti-viral guanine compounds

9-[2-(Hydroxymethyl)cycloalkylmethyl]guanines which are herpes simplex viral thymidine kinase inhibitors, their acyl derivatives, their phosphate derivatives and their pharmaceutically-acceptable salts; pharmaceutical formulations containing these compounds; the treatment of DNA viral, particularly herpes viral, infections with these compounds; methods of preparing these compounds; and novel intermediates useful in their preparation.

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New York, NY, United States of America

John D Karkas