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Synthesis and Antiviral Activity of 5′‐ O ‐(Substituted) Sulfamoyl Pyrimidine Nucleosides
Author(s) -
CastroPichel Julia,
GarcíaLópez M. Teresa,
de Las Heras Federico G.,
Herranz Rosario,
Pérez Concepción,
Vilas Pilar
Publication year - 1989
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19893220104
Subject(s) - chemistry , isopropyl , cytidine , pyrimidine , hydrolysis , stereochemistry , medicinal chemistry , acetylation , chloride , organic chemistry , biochemistry , enzyme , gene
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.