title: Synthesis and cytotoxic activity of carboxamide derivatives of benzo[b][1,6]naphthyridin-(5H)ones.
abstract: A previous reaction leading to 2-substituted 6-methyl-1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carboxylic acids has been extended to encompass a broad range of 2-substituents. Derived carboxamides, particularly 4-N-[2-(dimethylamino)ethyl], were tested for growth inhibitory properties. Potent cytotoxicity against murine P388 leukemia and Lewis lung carcinoma (LLTC) was retained for compounds bearing a remarkably diverse range of 2-substituents with a number having IC50 values <10 nM. Five of the new compounds were tested in vivo against subcutaneous colon 38 tumors in mice; a single dose (1.8 mg/kg) proved curative for the 2-(4-fluorophenyl) derivative, a further increase in potency over the very effective 2-methyl analogue reported previously.
authors.affiliation: Chemistry Department, La Trobe University, Victoria 3086, Australia. l.deady@latrobe.edu.au
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Deady
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rogers
authors.forename: Li
authors.initials: L
authors.lastname: Zhuang
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009287:Naphthyridines