[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-triazolo[1,5-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-triazolo[1,5-a]pyrimidine and 5-piperidin-4'-olyl-7-[N-pent-4-olyl-N-(beta-hydroxyet hyl)]amino-s- triazolo[1,5-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- triazolo[1,5-a]pyrimidine, no hydroxy derivatives of the bicyclic system were observed. The major part of unchanged 1 and metabolites is excreted via kidneys.
Pfeifer
S
S
Sektion Chemie, Humboldt-Universität zu Berlin.
Langner
A
A
Grahlmann
D
D
Franke
P
P
Gründemann
E
E
Tenor
E
E
D000327:Adsorption; D000818:Animals; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D014192:Trapidil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine
D014192:Trapidil; C053729:AR 12463
Biotransformation des Trapidil (Rocornal)-Derivates AR 12463 bei der Ratte.