Biotransformation of the trapidil (rocornal) derivative AR 12463 in the rat

After p.o. administration of 5-piperidino-7-N-pentyl-N-(beta- hydroxyethyl)]amino-s-triazolo1,5-a]pyrimidine (1; AR 12463) more than 15 metabolites were isolated from urine and feces of male Wistar rats. Only small amounts of unchanged 1 were observed. The structure of 12 metabolites was elucidated or proposed on the basis of UV-, 13C NMR- and mass spectra. Main metabolites are 5-piperidin-4'-olyl-7-N-pentyl-N-(beta- hydroxyethyl)]amino-s-triazolo1,5-a]pyrimidine and 5-piperidin-4'-olyl-7-N-pent-4-olyl-N-(beta-hydroxyet hyl)]amino-s- triazolo1,5-a]pyrimidine. The other metabolites are mainly hydroxy- or ketopentyl derivatives and piperidinoles or piperidinones, respectively. Conjugates of most of the metabolites were identified, but the ratio phase-I/II metabolites was about 3:1. In contrast to trapidil, 5-methyl-7-diethylamino-s- triazolo1,5-a]pyrimidine, no hydroxy derivatives of the bicyclic system were observed. The major part of unchanged 1 and metabolites is excreted via kidneys.