N-Mannich-base prodrugs of 5-iodo-2'-deoxycytidine as topical delivery enhancers.
Two Mannich-base prodrugs of 5-iodo-2'-deoxycytidine (5-IDC) have been synthesized. The prodrugs exhibit increased lipid solubility compared to 5-IDC and rapidly revert to 5-IDC in buffer. One of the prodrugs delivered about twice as much 5-IDC from isopropyl myristate (IPM) through hairless mouse skin in diffusion-cell experiments as did 5-IDC from IPM. Subsequent applications of theophylline/propylene glycol onto the diffusion cells to determine the effect of prodrug/IPM, 5-IDC/IPM, or IPM on the resistance of the skins to subsequent applications showed that the prodrug/IPM had no more effect than IPM itself.
D000287:Administration, Topical; D000588:Amines / Q000493:pharmacokinetics*; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001972:Bromodeoxycytidine / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004058:Diffusion; D006207:Half-Life; D008352:Mannich Bases / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D011355:Prodrugs / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D012995:Solubility
D000588:Amines; D000998:Antiviral Agents; D008352:Mannich Bases; D011355:Prodrugs; D003841:Deoxycytidine; D001972:Bromodeoxycytidine; C011288:ibacitabine