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.
Castro-Pichel
J
J
García-López
M T
MT
De las Heras
F G
FG
Herranz
R
R
Pérez
C
C
Vilas
P
P
D000998:Antiviral Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides