Substituted Pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones as Multidrug-Resistance Modulating Agents

• Published in: Journal of medicinal chemistry Vol. 47; no. 18; pp. 4627 - 4630
• Main Authors: Ott, Ingo, Kircher, Brigitte, Heinisch, Gottfried, Matuszczak, Barbara
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 26-08-2004
• Subjects: Antineoplastic agents; Biological and medical sciences; Cell Division - drug effects; Dibenzoxazepines - chemical synthesis; Dibenzoxazepines - pharmacology; Drug Resistance, Multiple - drug effects; General aspects; HeLa Cells; Humans; Ketones - chemical synthesis; Ketones - pharmacology; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; Vincristine - pharmacology; Antineoplastic agent; Human; Lactam; Tricyclic compound; Organic chlorine compounds; In vitro; Hela cell line; Biological activity; Cell line; Multiple resistance; Reversibility; Aromatic compound; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm040803n

Pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones substituted with propylene-linked basic side chains were synthesized and investigated for the ability to reverse multidrug resistance (MDR) at vincristine-pretreated HeLa-MDR1 cells. The substances were found to be effective chemosensitizers with activity comparable to that of the known MDR modulator verapamil. The observed antiproliferative effects were not caused by direct drug cytotoxicity.