Synthesis and Antitumor Evaluation of New Thiazolo[5,4-b]quinoline Derivatives

• Published in: Journal of medicinal chemistry 1997-02, Vol.40 (5), p.668-676
• Main Authors: Alvarez-Ibarra, Carlos, Fernández-Granda, Rocío, Quiroga, María L, Carbonell, Angélica, Cárdenas, Francisco, Giralt, Ernest
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Division - drug effects; Drug Screening Assays, Antitumor; General aspects; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Molecular Structure; Pharmacology. Drug treatments; Quinolines - chemical synthesis; Quinolines - pharmacology; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - pharmacology; Tumor Cells, Cultured
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm960556q

A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(ethoxycarbonyl)-5-(arylamino)thiazoles and 5-(arylamino)-4-carbamoylthiazoles, respectively, is described. In vitro cytotoxicity of a large number of derivatives of these compounds has been tested against several cell lines. The highest activities observed are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]amino] substituent at C-2 and a fluorine atom at the C-7 position of the tricyclic planar heteroaromatic framework. Three structural features seem to be essential for antitumor activities:  a positive charge density at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloquinoline skeleton with two basic nitrogens and a pK a value of 7.5−10 in the most basic center, and a conformational flexibility of this basic side chain. These structural requirements must be simultaneously satisfied in order to ensure a significant antitumor activity.