Synthesis and identification of the major metabolites of prazosin formed in dog and rat.
The 6-O-demethyl and 7-O-demethyl analogues of the new antihypertensive drug prazosin [2-[4-(2-furoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate ten-step reaction sequences starting from isovanillin and vanillin, respectively. The 6-O-demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7-O-demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline and 2,4-diamino-6,7-dimethoxyquinazoline, are also described. All four metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.
D000818:Animals; D000959:Antihypertensive Agents; D001647:Bile Acids and Salts / Q000032:analysis; D004285:Dogs; D008722:Methods; D011224:Prazosin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D011799:Quinazolines / Q000378:metabolism* / Q000652:urine; D051381:Rats
D000959:Antihypertensive Agents; D001647:Bile Acids and Salts; D011799:Quinazolines; D011224:Prazosin