Improved delivery through biological membranes VIII: Design, synthesis, and in vivo testing of true prodrugs of aspirin.
Novel activated ester-type prodrugs of aspirin were designed and synthesized. The methylthiomethyl, methylsulfinymethyl, and methylsulfonylmethyl esters of aspirin (acetylsalicylic acid) were cleaved in vitro in plasma to form aspirin rather than the corresponding salicylates. In vitro studies using dogs indicated that at least one aspirin derivative, methylsulfinylmethyl-2-acetoxybenzoate, is a true aspirin prodrug since aspirin was detected in the blood after prodrug administration.
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D005260:Female; D006868:Hydrolysis; D007700:Kinetics; D008566:Membranes / Q000378:metabolism
D001241:Aspirin