Antibacterial and/or antiprotozoal nitromidazole derivative compounds with urease inhibitor activity, process for preparing these compounds and use in pharmaceutical compositions and medicines

A process for preparing a compound of the formula (I)

• wherein:
• R1═NO2, R2═CH3 and R3═CH2, CHCH3, CHCH2Cl
• OR
• R1═H, R2═NO2 and R3═O(CH2)4, OCH2(CH)2CH2, OCH2—C═C—CH2, CHCH2OCH3, CONH(CH2)1-2,
• and
• CH2CO, wherein n=1-6
• R5═NHCONH2, NHCONHOH, ONHCONHOH, OCH2NHCONHCH2OH, NHCSNH2, NHCSNHOH, ONHCSNHOH, OCH2NHCSNHCH2OH, NHCNHNH2, NHCNHNHOH, ONHCNHNHOH, OCH2NHCNHNHCH2OH
• which comprises reacting a compound of formula (III)
• wherein R1, R2, R3, R4 are described above and X═OH or Cl, with an urease affinity compound selected from the group consisting of urea, N-hydroxyurea, N,N′-dihydroxyurea, bis-(hydroxymethil)urea, thiourea, N-hydroxythiourea, N,N′-dihydroxythiourea, bis-(hydroxymethyl)thiourea, guanidine, N-hydroxyguanidine, N,N′-dihydroxyguanidine and bis-(hydroxymethyl)guanidine.

A compound selected from the group consisting of:

• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-[(aminocarbonothioyl)amino]-4-oxobutanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-[(aminocarbonyl)amino]-4-oxobutanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-{[amino(imino)methyl]amino}-4-oxobutanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-{[(hydroxyamino)carbonothioyl]amino}-4-oxobutanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-{[(hydroxyamino)carbonyl]amino}-4-oxobutanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-{[(hydroxyamino)(imino)methyl]amino}-4-oxobutanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 5-[(aminocarbonothioyl)amino]-5-oxopentanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 5-[(aminocarbonyl)amino]-5-oxopentanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 5-{[amino(imino)methyl]amino}-5-oxopentanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 5-{[(hydroxyamino)carbonothioyl]amino}-5-oxopentanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 5-{[(hydroxyamino)carbonyl]amino}-5-oxopentanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 5-{[(hydroxyamino)(imino)methyl]amino}-5-oxopentanoate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl {2-[(aminocarbonothioyl)amino]-2-oxoethoxy}acetate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl {2-[(aminocarbonyl)amino]-2-oxoethoxy}acetate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl (2-{[amino(imino)methyl]amino}-2-oxoethoxy)acetate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl (2-{[(hydroxyamino)carbonothioyl]amino}-2-oxoethoxy)acetate;
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl (2-{[(hydroxyamino)carbonyl]amino}-2-oxoethoxy)acetate;
• and
• 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl (2-{[(hydroxyamino)(imino)methyl]amino}-2-oxoethoxy)acetate;
• or their pharmaceutically acceptable salts.

A method for treating a bacterial or parasitic infection comprising administering to a subject infected by a bacterium or parasite an effective amount of a pharmaceutical composition comprising a compound of the formula (I)

• wherein:
• R1═NO2, R2═CH3 and R3═CH2, CHCH3, CHCH2Cl
• OR
• R1═H, R2═NO2 and R3═O(CH2)4, OCH2(CH)2CH2, OCH2—C═C—CH2, CHCH2OCH3, CONH(CH2)1-2,
• and
• CH2CO, wherein n=1-6
• R5═NHCONH2, NHCONHOH, ONHCONHOH, OCH2NHCONHCH2OH, NHCSNH2, NHCSNHOH, ONHCSNHOH, OCH2NHCSNHCH2OH, NHCNHNH2, NHCNHNHOH, ONHCNHNHOH, OCH2NHCNHNHCH2OH.