65917-65-9Relevant academic research and scientific papers
Nitroimidazoles: Part XV - 1-Methyl-5-nitro-2-oxy(mercapto)imidazoles, 1-Methyl-5-nitroimidazole-2-methanol (carboxaldehydes and glyoxalic ester) Derivatives and 1-Substituted Alkyl 2-Methyl-5 and 4-nitroimidazoles
Arya, V. P.,Nagarajan, K.,Shenoy, S. J.
, p. 1078 - 1086 (2007/10/02)
Treatment of 1-methyl-2-methylsulphonyl-5-nitroimidazole (2) with p-hydroxybenzaldehyde gives the aldehyde (3a) which is derivatised further to 3b-d.Displacement reactions on 2 with other phenols affords 4a-c. 1-Methyl-2-mercaptoimidazole (5a) is condensed with reactive halides to form sulphides 5b-e which are nitrated further to lead to nitroimidazoles 6a-d among which 6a and 6d undergo oxidation to form sulphone (7a) and sulphoxide (8) respectively; some nitroimidazolyl sulphides (6e-h) are also prepared from 2 by displacement with thiophenol salts. 6f is further oxidised to 7b. 1-Methyl-5-nitroimidazole-2-methanol (9a) is converted into sulphate esters (9b and 9c), chloride (9d), urethanes (10a-e) and amines (11a-c). 1-Methyl-5-nitroimidazole-2-aldehyde (12a) is characterised as the hydrazones (12b-f) and the vinyl derivatives (13a-f) and (14).Reactions of 1-methyl-5-nitroimidazole (15) with ethoxalyl and oxalyl chlorides yield 16a and 19 respectively. 16a is further reacted with aminoguanidine to yield 18.Metronidazole (22a) is transformed into the urethane (22b) and via the chloride (22c) into the bases (22d-g).Ornidazole (23a) likewise affords the amines (23b and c) while the isomer 24a yields 24b-g.Alkylation of the sodium salts of 4-nitro and 4-nitro-2-methylimidazole with 3-chloro-4-hydroxysulpholane (25) provides the 4-nitro derivatives (26a) and (26b).Reaction of 2-bromo-1-indanol with 2-methyl-4-nitroimidazole does not provide 28, but 30, for which a mechanism is proposed.
Chemotherapeutically active nitro compounds, 4, 5-nitroimidazoles (part I)
Winkelmann,Raether,Gebert,Sinharay
, p. 2251 - 2263 (2007/10/05)
More than 135 new 2-methyl-5-nitroimidazoles substituted in 1-position and 1-methyl-5-nitroimidazoles substituted in 2-position were investigated for their activity against various protozoan species, in particular Entamoeba histolytica in the golden hamster, Trichomonas fetus, Trypanosoma brucei and T. cruzi in the NMRI mouse. Among the nitroimidazoles substituted in the 1-position only two preparations exhibited a similar effect as metronidazole against T. fetus. In the class of the nitroimidazoles substituted in the 2-position 16 compounds were as effective as metronidazole, 19 showed an effect superior to metronidazole, 1 was as good as tinidazole and 2 exhibited an activity superior to tinidazole against T. fetus. Only few compounds displayed any amoebicidal activity. Of the mono and bis-hydrazones of 1-methyl-5-nitroimidazole-2-aldehyde substituted in the 2-position 3 compounds had an amoebicidal effect 2 to 8 times stronger than that of metronidazole. Only few representatives of the 1-methyl-5-nitroimidazoles substituted in the 2-position produced a useful trypanocidal effect when given in relatively high doses. The structure-activity relationship of 5-nitroimidazole derivatives has been discussed.
