ETHYL 4(5)-IMIDAZOLECARBOXYLATE (CODE NO. C-751) AS AN ORALLY EFFECTIVE CHEMOTHERAPEUTIC AGENT AGAINST LEPTOSPIROSIS

938 compounds were tested against experimental leptospirosis on hamsters in a joint screening program launched between 1969-1973. Attention was later focussed on imidazole derivatives from which compounds with the basic structure as depicted in the formula where R=H, OH, OAlkyl, or NHwere found to be active. The structure-activity relationship （SAR） was discussed.Ethyl 4（5）-imidazolecarboxylate （Code No. C-751） was selected for further studies in experimental therapy, it was shown to be highly effective in protecting from death golden hamsters challenge with lethal doses of L. icterohaemorrhagiae Lai strain and L. canicola. However, its action was essentially inhibitive in nature.The drug disappeared rapidly from the gastrointestinal tract and was present as such in the blood. It was rotund to cross the blood brain barrier readily, undergo partial hydrolysis in the liver and largely eliminated through the kidney. Urinary excretion in the first 24 hours after administration accounted for most part of C-751 and its metabolite excreted.The drug was found to have low toxicity and to be well tolerated. Clinical trials have fully substantiated its therapeutic effectiveness against leptospirosis in man caused by L. icterohaemorrhagiae, L. grippotyphosa, L. autumnalis, L. canicola, L. pyrogenes, L. hyos, L. pomona, L. javanica, and L. australis.Clinical trials were carried out on 202 cases of leptospirosis. 201 cases were cured.