Arthur G Field Deceased274 Confederate Cir, Charleston, SC 29407

4816447, Mar 28, 1989

Jun 6, 1984

6/617868

Wallace T. Ashton - Clark NJ
Arthur K. Field - North Wales PA
John D. Karkas - New York NY
Richard L. Tolman - Warren NJ

Merck & Co., Inc. - Rahway NJ

C07D47318
A61K 3152

514 81

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.

4880820, Nov 14, 1989

Feb 8, 1988

7/150478

Wallace T. Ashton - Clark NJ
Laura F. Canning - Clark NJ
Arthur K. Field - North Wales PA
Richard L. Tolman - Warren NJ

Merck & Co., Inc. - Rahway NJ

C07D47318
A61K 3152

514322

(S)-9-(2,3-dihydroxy-1-propoxymethyl)guanine has potent antiherpetic activity which is superior to the corresponding racemic mixture or the (R)-enantiomer and also is much more potent than 9-(2-hydroxyethoxymethyl)guanine. Acyl derivatives (prodrugs) of the (S)-enantiomer, which are more effective than the corresponding (R)-enantiomer analogs or related racemic mixtures provide formulation advantages and even higher plasma half lives in animals or man than the (S)-isomer.