ALPHA-TRIFLUOROMETHYL-BETA-UREIDO-PROPIONIC ACID (F3MUPA) - A NEW METABOLITE OF TRIFLURIDINE (F3TDR)

The metabolism of 5-trifuluro-2'-deoxythymidine (trifluridine; F3TdR) in male BALB/c mice bearing EMT-6 tumors has been investigated using F -19 NMR spectroscopy. We previously (Tandon et al, 1992) reported the detection and identification of 5,6-dihydro-5-trifluorothymine (DHF3T, 3 underbar) and 5,6-dihydroxy-5-trifluorothymine (DOHF3T) as new meta bolites of F3TdR in mice urine. Further exploration of the metabolism of trifluridine has led to the identification of alpha-trifluoromethyl -beta-ureido-propionic acid (F3MUPA, 4 underbar) as a previously unrep orted metabolite in the urine of F3TdR treated mice. Authentic F3MUPA was obtained by synthesis via an established route. A comparison of ch emical shift and the H-F coupling constant of an authentic sample, wit h the F-19 signal from urine, indicated the presence of F3MUPA in muri ne urine. Mixing crude urine with authentic F3MUPA resulted in the enh ancement of the corresponding fluorine signal without affecting or int roducing others, thereby confirming the presence of F3MUPA as a urinar y metabolite.