Potential antitumor agents. 21. Structure determination and antitumor activity of imidazo[2,1-b]thiazole guanylhydrazones

Journal of Medicinal Chemistry
1992.0

Abstract

In the course of the past 25 years, guanylhydrazones have been reported in the literature as antiprotozoal, antibacterial, antidepressive, antiinflammatory, platelet aggregation inhibiting, antihypertensive, antiviral, antiarrhythmic, cardiotonic, and antimitotic or antitumor agents. This last aspect is the most interesting for us since we have devoted a large part of our research efforts to the synthesis of potential antitumor agents; in particular, some of our previous papers were related to hydrazone derivatives of indoles and imidazo[2,1-b]thiazoles. The history of hydrazone derivatives as antitumor agents begins in 1956 when R. W. Brockman et al. reported the antileukemic activity of pyridine-2-carboxaldehyde thiosemicarbazone. Two years later the antileukemic activity of glyoxal bisguanylhydrazone was reported. These two works stimulated numerous papers. While the research in this field is still very active, mitoguazone and ambazone are under clinical trials, and bisantrene is commercially available in France under the name of Zantrene. In connection with the aforementioned considerations, we now wish to report the synthesis of a series of guanylhydrazones (see Table I) from imidazo[2,1-b]thiazoles (1-5) and thiazolines (6-10) bearing a substituent at position 6. The aim of this work is to study the effect of the antitumor activity of this substituent and of the double bond at position 2,3.

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