Synthesis and analysis of urea and carbamate prodrugs as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT).
The suitability of 4-di(2-chloroethyl)aminoanilino-4-hydroxyphenethylaminomethanone 2 to act as a prodrug for melanocyte-directed enzyme prodrug therapy (MDEPT) is assessed. Thus its synthesis, ability to generate a cytotoxic agent upon exposure to tyrosinase, and stability within different sera are reported. A comparison is made to illustrate that the new urea prodrug 2 is a more suitable candidate for MDEPT than the corresponding carbamate prodrug 1.
Jordan
Allan M
AM
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK.
Khan
Tariq H
TH
Malkin
Hugh
H
Osborn
Helen M I
HM
D000818:Animals; D001769:Blood; D002219:Carbamates / Q000138:chemical synthesis / Q000627:therapeutic use; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems; D004355:Drug Stability; D057487:Enzyme Therapy; D006801:Humans; D008544:Melanocytes / Q000187:drug effects*; D014442:Monophenol Monooxygenase / Q000378:metabolism / Q000627:therapeutic use; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000627:therapeutic use
D002219:Carbamates; D011355:Prodrugs; D014508:Urea; D014442:Monophenol Monooxygenase