Nitrendipine: identification and synthesis of main metabolites.
(+/-)-Ethylmethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (nitrendipine, Bay e 5009) 1, a calcium antagonistic 1,4-dihydropyridine derivative, is currently under development as an antihypertensive. A pharmacokinetic study with 14C-nitrendipine in the rat revealed as major metabolites the pyridine 2, 3, 4, 5, 6 and 9 using glc-, tlc- and gc/ms-techniques. A potential metabolic pathway is discussed involving oxidation to the pyridine form, saponification of the ester groups and hydroxylation of the methyl groups as general biotransformation steps. 1,4-Dihydropyridines bearing appropriate functionalities were precursors in the synthesis of the reference metabolites 2, 3, 4, 7, 8 and 10.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D005243:Feces / Q000032:analysis; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains
D009568:Nitrendipine; D009543:Nifedipine