Synthesis and antiviral activity of 5'-O-(substituted) sulfamoyl pyrimidine nucleosides

5′-O-[N-(Aminoacyl or isobutyryl)sulfamoyl]uridines 4a-e, 5a-e and 5′-O-[N-(isopropyl)sulfamoyl]cytidines 7–9 have been synthesized and tested against herpes simplex virus type 2. Condensation of 2′,3′-O-isopropylidene-5′-O-sulfamoyluridine with the N-hydroxysuccinimide esters of Boc-Gly, Boc-L-Ala, Boc-D-Ala and Boc-L-Phe, gave 4a-d which, on deprotection under acidic conditions, provided 5a-d. A similar condensation of 2′,3′-di-O-acetyl-5′-O-sulfamoyluridine with the N-hydroxysuccinimide ester of isobutyric acid afforded 4e which on deacylation led to 5e. 5′-O-[N-(Isopropyl)sulfamoyl]-2′,3′-O-isopropylidenecytidine (7) was prepared by reaction of 2,3′-O-isopropylidene-4-N-[(dimethylamino)methylene] cytidine with N-isopropylsulfamoyl chloride. Acidic hydrolysis of 7 provided 8 which, upon acetylation, gave the corresponding 2′,3′-di-O-acetyl derivative 9. Compounds 7–9 show antiviral effect. Structure-activity relationships are discussed