Synthesis and cytotoxic activity of (E) -1- (2-nitrovinyl) and 1-[N- (tert-butylformiminyl) ]-substituted 1,4-dihydropyridines and 2-pyridones
Im, C.; Knaus, E.E.; Thuynsma, R.P.; Allen, T.M.
Drug Design and Delivery 5(3): 239-248
1990
ISSN/ISBN: 0884-2884 PMID: 1670504 Document Number: 362216
1-(2-Nitrovinyl) derivatives of nuclear substituted 1,4-dihydropyridines (7a-c), and 1-(N-tert-butyl-formiminyl) derivatives of 1,4-dihydropyridines (9a-c) or 2-pyridones (11a-c) were synthesized for evaluation as cytotoxic agents (see Table I for structures). The in vitro cytotoxic activities, determined in the L1210 assay, indicated that the 4-substituent on a 1,4-dihydropyridine ring system was a determinant of activity in both the 1-(2-nitrovinyl) (7) and 1-(N-tert-butylformiminyl) (9) series, the relative activity order being n-Bu > Ph > Me. In the 1-(N-tert-butylformiminyl) series, the 1,4-dihydropyridine derivatives (9) were generally more cytotoxic than the 2-pyridone derivatives (11). The most active compound was 1-(N-tert-butylformiminyl)-3-(4,4-dimethyloxazolin-2-yl)-4-n -butyl-1,4- dihydropyridine (9b), but it was 2-3 log units less active than the reference standard melphalan.