title: Synthesis and cytotoxic activity of carboxamide derivatives of benzo[b][1,6]naphthyridines.
abstract: The reaction of 4-dimethylaminomethylene-6-methyl-4H-pyrano[4,3-b]quinoline-1,3-dione with a range of primary amines gave rise to a series of 2-substituted 6-methyl-1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carboxylic acids. The derived 4-N-[2-(dimethylamino)ethyl]carboxamides were tested for growth inhibitory properties against murine P388 leukemia, Lewis lung carcinoma (LLTC), and human Jurkat leukemia cell lines. Most compounds were potent cytotoxins, with some having IC(50) values less than 10 nM. Five were tested in vivo against subcutaneous colon 38 tumors in mice, and a single dose (3.9 mg/kg) proved to be curative for the 2-methyl and 2-(3,4-dimethoxyphenyl) derivatives in this refractory model.
authors.affiliation: Chemistry Department, La Trobe University, Victoria 3086, Australia. b.denny@auckland.ac.nz
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Deady
authors.forename: Thomas
authors.initials: T
authors.lastname: Rodemann
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; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009287:Naphthyridines