Premium
Synthesis and biodistribution of p ‐iodophenyl analogues of a naturally occurring imidazole ribonucleoside
Author(s) -
Suggs Jennifer A.,
Srivastava Prem C.
Publication year - 1988
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570250512
Subject(s) - ribonucleoside , chemistry , biodistribution , imidazole , stereochemistry , acetylation , carboxamide , rna , biochemistry , in vitro , gene
A model iodophenyl imidazole ribonucleoside has been synthesized to study biodistribution properties in laboratory animals. The key intermediate 5‐amino‐1‐(2,3,5‐tri‐ O ‐acetyl‐β‐D‐ribofuranosyl)imidazole‐4‐[ N ‐( p ‐iodophenyl)carboxamide] ( 5 ) was synthesized by coupling N ‐succinimidyl‐5‐amino‐1‐(2,3,5‐tri‐ O ‐acetyl‐β‐D‐ribofuranosyl)imidazole‐4‐carboxylate ( 4 ) and p ‐iodoaniline. Deacetylation of the intermediate compound gave 5‐amino‐1‐β‐D‐ribofuranosylimidazole‐4‐[ N ‐( p ‐iodophenyl)]carboxamide ( 6 ). Ring annulation via diazotization of 5 gave 7‐(2,3,5‐tri‐ O ‐acetyl‐β‐D‐ribofuranosyl)imidazo[4,5‐ d ]‐ v ‐triazin‐[3‐ N ‐( p ‐iodophenyl)]‐4‐one ( 7 ). Subsequent deacetylation of 7 afforded 7‐β‐D‐ribofuranosylimidazo[4,5‐ d ]‐ v ‐triazin‐[3‐ N ‐( p ‐iodophenyl)]‐4‐one ( 8 ). The radiolabeled compounds, [ 125 I] 5 and [ 125 I] 6 were prepared in a manner similar to the corresponding unlabeled compounds except that p ‐[ 125 I]iodoaniline was used for coupling with 4 . Biodistribution studies of iodine‐125‐labeled 5 and 6 were performed in female Fischer rats and tumor bearing nude mice. Compound 6 showed uptake in the brain and proliferating tissues such as tumor and bone‐marrow.