Chemical and biological degradation of 5-fluorouracil prodrugs having high serum albumin binding potencies.
In order to understand the fundamental structural features which yield both high serum albumin binding potency and desired property as a prodrug, the derivatization was performed at N-1 or N-3 position in 5-fluorouracil. The N-3 derivatives were more stable than N-1 derivatives in vitro, whereas they were metabolized quickly in vivo. It is suggested that N-1 position should be blocked to avoid fast metabolism in vivo.
Suda
Y
Y
Department of Chemistry, Faculty of Science, Osaka University, Japan.
Shimidzu
K
K
Sumi
M
M
Kusumoto
S
S
Nadai
T
T
Yamashita
S
S
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
D011355:Prodrugs; D012709:Serum Albumin; D005472:Fluorouracil