SYNTHESIS AND ANTITUMOR EVALUATION OF NEW THIAZOLO[5,4-B]QUINOLINE DERIVATIVES

A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinoli nes 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 observe d are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]am ino] 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 densi ty at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloq uinoline 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 ba sic side chain. These structural requirements must be simultaneously s atisfied in order to ensure a significant antitumor activity.