title: Synthesis and cytotoxic activity of 1-(3-oxoprop-1-enyl)-2-pyridones.
abstract: 1-(3-Oxoprop-1-enyl) derivatives of nuclear substituted 2-pyridones (7a-i), 2-pyridinethione (7j), 1-isoquinolone (9), and the 1,4-dihydropyridine (11) have been synthesized and tested for biological activity. The 2-pyridones (7) and the 1-isoquinolone (9) were all active cytotoxic agents as determined in the in vitro L1210 screen, exhibiting activity in the ED50 0.5-3.5 micrograms/ml range. The nature and position of nuclear substituents present in 7 and 9 did not alter activity significantly. The unsubstituted (7a) and 5-ethoxycarbonyl-2-pyridones (7g), and the 1-isoquinolone derivative (9) were active antineoplastic agents (%T/C = 133-135) in vivo exhibiting activity comparable to 5-fluorouracil.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: L K
authors.initials: LK
authors.lastname: Ho
authors.forename: E E
authors.initials: EE
authors.lastname: Knaus
authors.forename: T M
authors.initials: TM
authors.lastname: Allen
authors.forename: R
authors.initials: R
authors.lastname: Fathi-Afshar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000473:pathology; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D011728:Pyridones