Antitumour Benzothiazoles. Part 15: The Synthesis and Physico-Chemical Properties of 2-(4-Aminophenyl)benzothiazole Sulfamate Salt Derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 8; pp. 1093 - 1095
• Main Authors: Shi, Dong-Fang, Bradshaw, Tracey D, Chua, Mei-Sze, Westwell, Andrew D, Stevens, Malcolm F.G
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 23.04.2001
• Subjects: Amines - chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzothiazoles; Breast Neoplasms - drug therapy; Drug Stability; Enzyme Activators - chemical synthesis; Enzyme Activators - chemistry; Enzyme Activators - pharmacology; Female; Guanylate Cyclase - drug effects; Guanylate Cyclase - metabolism; Humans; Hydrogen-Ion Concentration; Inhibitory Concentration 50; Platelet Aggregation Inhibitors - chemical synthesis; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Prodrugs - chemistry; Prodrugs - pharmacology; Solubility; Sulfonic Acids - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Tumor Cells, Cultured - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00142-1

A series of sulfamate salt derivatives of the potent and selective 2-(4-aminophenyl)benzothiazole antitumour agents has been prepared and their evaluation as potential prodrugs for parenteral administration carried out. The salts were sparingly soluble under aqueous conditions (pH 4–9), and degradation to the active free amine was shown to occur under strongly acidic conditions. The salts were found to be markedly less active than their parent amines against sensitive human tumour cell lines in vitro. A series of sulfamate salt derivatives of the potent and selective 2-(4-aminophenyl)benzothiazole antitumour agents has been prepared and their evaluation as potential prodrugs for parenteral administration carried out.