A new reversible transformation of oxindolylidene derivatives of imidazothiazolotriazine into 3-[(imidazotriazin-3-yl)thio]-2-oxoquinoline-4-carboxylates

Abstract

A simple method for the synthesis of water-soluble potassium 3-[(imidazotriazin-3-yl)thio]-2-oxoquinoline-4-carboxylates was developed based on a new reversible transformation of oxindolylidene derivatives of imidazothiazolotriazine that results from their treatment with potassium hydroxide. The antiproliferative activity of the synthesized compounds was evaluated against 58 cell lines and compared with oxindolylidene derivatives of imidazothiazolotriazine. Quinoline derivatives 3 demonstrated high activity with average GI₅₀ values of <10 μM which are comparable or higher than those of the oxindolylidene imidazothiazolotriazines. Compound 3a, with a pent-3-yl substituent at the nitrogen atom of the quinoline fragment, possessed the highest antiproliferative activity with an average GI₅₀ value of 1.71 μM. The GI₅₀ values of compound 3a against 52 of the 58 cell lines were <1 μM; against the remaining 6 of the 58 cell lines, they were in the range 1.21–39.2 μM.