GB1006334A - Imidazole derivatives - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:1006334/C2/1> wherein R1 represents an alkyl group containing up to 6 carbon atoms and R2 represents a hydrogen atom or an alkanoyl group containing up to 6 carbon atoms, and acid addition salts thereof. The compounds may be prepared by a variety of methods, (1) by alkylation of a compound <FORM:1006334/C2/2> by reaction with an alkyl ester R1X where X is an acid residue of a reactive ester, e.g. halide, sulphate or sulphonate, the compound II being obtained by nitration of <FORM:1006334/C2/3> (2) by nitration of a compound <FORM:1006334/C2/4> and isolating the desired nitroimidazole isomer, the compound III being obtained by alkylation of compound VI or, when R2 is a hydrogen atom, by reacting a compound VII <FORM:1006334/C2/5> with formaldehyde under pressure, (3) by reaction of a compound <FORM:1006334/C2/6> with a compound MOR2, wherein M is an alkali metal, the compound IV being obtained by treating a compound <FORM:1006334/C2/7> with a reagent which introduces the group X, e.g. halogenation, (4) by dequaternization, e.g. by heating, a compound <FORM:1006334/C2/8> wherein R3 is an alkyl group containing up to 6 carbon atoms and Y is halogen, which is obtained by reaction of a compound <FORM:1006334/C2/9> with R1Y, and (5), when R2 is a alkanoyl group, by acylation of those compounds of formula (I) in which R2 is hydrogen, e.g. with an acid anhydride. Example 1 and 2 describes the preparation of 2-hydroxymethyl-1-methyl-5-nitroimidazole and 2-acetoxy-methyl-1-methyl-5-nitroimidazole respectively. The invention includes pharmaceutical compositions possessing, particularly, antiprotozoal and antibacterial activity, which comprise at least one of the compounds of formula (1) or a non-toxic acid addition salt thereof and which may be administered orally, parenterally or topically in the form of compressed tablets, pills, dispersible powders, granules, emulsions, solutions, suspensions, syrups, elixirs, capsules of absorbable material, creams, ointments, lotions, pessaries and ovales. Example 3 describes the preparation of tablets containing 2 - hydroxymethyl - 1 - methyl - 5 - nitroimidazole.