Chemotherapeutically active nitro compounds. 4.5-Nitroimidazoles (Part II)

More than 170 1-methyl-5-nitroimidazoles substituted in the 2-position via an aminomethyl, thiomethyl, sulphinylmethyl or sulphonylmethyl group were synthesized and tested for their effect against various protozoa. In the NMRI mouse which had been i.p. infected with Trichomonas fetus 2 compounds showed an effect superior to that of tinidazole and 31 showed similarly good efficacy as that compound. In comparison with metronidazole 54 preparations proved to be distinctly more active, while 34 others lay in the range of efficacy of the standard compound. A large majority of the most active derivatives is substituted in the 2-position via a C--S bridge with heterocyclics, particularly with a pyridyl radical. An effect against Entamoeba histolytica in the intrahepatically infected golden hamster was observed much less often. Only 14 preparations developed a systemic effect comparable with that of metronidazole. In the NMRI mouse infected i.p. with Trypanosoma brucei or s.c. with T. cruzi parasitemia was clearly influenced by 11 compounds. With a few exceptions a trypanocidal effect against T. brucei occurred only at high doses. Only 3 compounds showed pronounced suppressive activity against blood forms of T. cruzi and only after prolonged treatment. The structure-activity relationship of the new 5-nitroimidazoles is discussed.