New imidazolylthiocarbamides as guanine deaminase inhibitors

Guanine deaminase is an important enzyme of purine catabolism which irreversibly deaminates guanine (1) to xanthine (2) and also 8-azaguanine to 8-azaxanthine. 8-Azaguanine is a carcinostatic agent whereas 8-azaxanthine is non-carcinostatic. It has been proposed that the selective action of thioguanine and 8-azaguinine on certain tissue is due to lack of guanine deaminase in these susceptible cell lines. Inhibitors of guanine deaminase are important because it is reasonable to postulate that it will inhibit the conversion of 8-azaguanine to 8-azaxanthine and these could be used with advantage along with thioguanine and 8-azaguanine. This paper reports synthesis of new imidazolylthiocarbamides as guanine deaminase inhibitors.