Effects of 5'-ester modification on the physicochemical properties and plasma protein binding of 5-iodo-2'-deoxyuridine.
A series of 5'-(O-acyl and O-benzoyl) derivatives of 5-iodo-2'-deoxyuridine (IDU) was synthesized by direct acylation of the parent nucleoside in a pyridine-N,N'-dimethylformamide mixture (1:1). Aqueous solubilities in phosphate buffer (pH 7.4), partition coefficients in 1-octanol/phosphate buffer (pH 7.4), plasma protein binding properties, and plasma reversion kinetics of these potential prodrugs were evaluated. The esters showed an expected increase in lipophilicity with a corresponding decrease in aqueous solubility relative to the parent compound. The association constants (Ka) with albumin also exhibited a good linear correlation with the lipophilicity of the compounds. However, the reversion rate constants in plasma varied with the steric and polar nature of the acyl or benzoyl substituent.
Ghosh
M K
MK
Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Mitra
A K
AK
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000378:metabolism; D011355:Prodrugs / Q000032:analysis / Q000138:chemical synthesis; D011485:Protein Binding; D051381:Rats; D012995:Solubility
D001798:Blood Proteins; D011355:Prodrugs; D007065:Idoxuridine