Author/Authors :
Kazuo Hattori، نويسنده , , Yasunori Kohchi، نويسنده , , Nobuhiro Oikawa، نويسنده , , Hitomi Suda، نويسنده , , Masako Ura، نويسنده , , Tohru Ishikawa، نويسنده , , Masanori Miwa، نويسنده , , Mika Endoh، نويسنده , , Hiroyuki Eda، نويسنده , , Hiromi Tanimura، نويسنده , , Akira Kawashima، نويسنده , , Ikuo Horii، نويسنده , , Hideo Ishitsuka، نويسنده , , Nobuo Shimma، نويسنده ,
Abstract :
A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues by sequential conversion of 11c by three enzymes: esterase, cytidine deaminase and thymidine phosphorylase, the latter two of which are known to be highly expressed in various tumor tissues. When capecitabine (1), a tumor-activated prodrug of 5-FU, was co-administered orally with 11c, 5-FU in tumor tissues was significantly increased with only a slight increase of 5-FU in plasma as compared with oral capecitabine alone.
