4 -5-nitroimidazole derivatives

Benznidazole, a nitroimidazole derivative, has a mode of action that seems to involve covalent modification of macromolecules by nitroreduction intermediates. 

G. lamblia is treated with 5-nitroimidazole derivates. Paromomycin is a second choice in specific circumstances (e.g. pregnancy). In a Cochrane review, where 34 trials were included and where only one trial was without significant methodological flaws, the authors concluded that a single dose of tinidazole can provide the highest clinical cure rate with relatively few adverse effects. The high recun ence rate of disease after initial diug therapy is a problem. 

Several studies have reported the influence of nitroimidazole derivatives on biological systems. Thus the influence of Misonidazole, l-(2-nitro-l-imidazoyl)-3-methoxy-propan-2-ol, on strand breaking in calf thymus DNA under ionizing radiation conditions has been assessed70. Pulse-radiolysis studies of nitroheterocyclic compounds have examined... 

Azomydn (nitroimidazole] derivatives, such as metronidazole, damage Ltillmann, Color Atlas of Pharmacology... 

Hypersensitivity to metronidazole or other nitroimidazole derivatives pregnancy (first trimester in patients with trichomoniasis). 

Hypersensitivity to tinidazole, any component of the tablet, or other nitroimidazole derivatives during the first trimester of pregnancy (see Warnings). 

NHE, which is a strong enough oxidant to abstract an electron from dG (i ° = 1.29 V vs. NHE ) to yield G +. Following deprotonation of G + to yield the neutral radical G(—H), reaction with N02 produces 8-nitro-dG and the 5-guanidino-4-nitroimidazole derivative (NI) following attachment of N02 at C-5 of G(—H) (Scheme 4). ... 

Another topical antibiotic, metronidazole, is effective in the treatment of acne rosacea. Metronidazole is a synthetic nitroimidazole derivative that reduces inflammation by an unknown mechanism. Other selected topical antibiotics are listed in Table 41.2. 

Chemical Class Nitroimidazole derivative Clinical Pharmacology ... 

Mechanism of Action A nitroimidazole derivative that disrupts bacterial and protozoal DNA, inhibitingnucleicacidsynthesis.Therapeutic E/fcct Produces bactericidal, ID-antibacterial, amebicidal, and trichomonacidal effects. Produces anti-inflammatory and immunosuppressive effects when applied topically. 

Contraindications Hypersensitivity to other nitroimidazole derivatives (also para-bens with topical application)... 

Mecfianism of Action A nitroimidazole derivative that is converted to the active metabolite by reduction of cell extracts otTricfiomonas. The active metabolite causes DNA damage in pathogens. Therapeutic Effect Produces antiprotozoal effect. Pharmacokinetics Rapidly and completely absorbed. Protein binding 12%. Distributed in all bodytissues and fluids crosses blood-brain barrier. Significantly metabolized. Primarily excreted in urine partially eliminated in feces. Half-life 12-14 hr. 

It is 5-nitroimidazole derivative with properties similar to metronidazole and... 

It is a 5-nitroimidazole derivative with the same antimicrobial profile as that of metronidazole, except that it has a much longer half-life. 

Meingassner JG, Mieth H (1976) Cross-resistance of trichomonads to 5-nitroimidazole derivatives. Experientia 32 183-184... 

Yarlett N, Yarlett NC, Lloyd D (1986b) Ferredoxin-dependent reduction of nitroimidazole derivatives in drug-resistant and susceptible strains of Trichomonas vaginalis. Biochem Pharmacol 35 1703-1708... 

The structure of nitroimidazoles has been studied more thoroughly and can be explained by wide application of these compounds, especially in medicine. In Table 3.3 some structural characteristics (X-ray and neutron study) for the imidazole and 2-nitroimidazole derivatives are given. 

Table 3.4 Bond lengths (A) and valence angles (°) in nitroimidazole derivatives... 

X-ray studies were also performed for bis(l,2,3,5-tetramethyl-4-nitropyrazolium salt [105], l-methyl-4(5)-nitro-5(4)-styrylimidazole [82], I -(/V-morpholino )-4-nitroimidazole [83], 1-sodium salt of 4-[2-[(l-methyl-5-nitro-2-imidazolyl)thio] ethoxy]-benzoic acid [106], l-methyl-4-nitro-5-chloroimidazole [107], omidazole [81], megazole [108], l-methyl-2-nitro-5-vinylimidazole [42], l-[2-(ethylsulfonyl) ethyl]-2-methyl-5-nitroimidazole (tinidazole) and one of the basic tinidazole metabolites - ammonium salt of l-[2-(ethylsulfonyl)ethyl]-4, 5-dihydro-2-methyl-4-nitroimidazole-5on [109], morpholino nitroimidazole derivatives [110, 111], l-(2-bromoethyl)-2-methyl-5-nitroimidazole [112], l-(4-chlorophenacyl)-2-methyl-... 

Some Indian researchers made use of NMR spectroscopy for the identification of compounds during the synthesis of a large series of nitroimidazole derivatives possessing many valuable properties [321, 380,429 1411. Suwinski and coworkers have investigated a large amount of different nitroimidazoles used in tumor radiotherapy or as tuberculosis inhibitors [442 151],... 

S atranidazole (1 -methylsulfonyl-3 -(1 -methyl-5-nitro-2-imidazolyl)-2-imidazo-lidinone) is reduced more easily at pH 7 and is more sensitive to pH than other nitroa-zoles (Table 3.42). Based on the comparison of the reduction potentials of satranidazole (at pH 7) with the potentials of 5-nitro- and 2-nitroimidazole derivatives and on the... 

On EC reduction, ionization of the N-H bond of nitroimidazole derivatives in buffer solutions (pH 7.0-7.4) occurs (Table 3.46) (Scheme 3.38) [919, 927-929], The anions formed are reduced to radical dianions. As should be expected, N-H nitroimidazoles are more difficult to reduce than A-substituted ones (not exposed to ionization) (Table 3.46) [928],... 

It is offered a polarographic method for the determination of the nitro group position in 4- and 5-nitroimidazole derivatives [953],... 

Nitroimidazole derivatives possess a very broad spectrum of practical application in medicine [25-30], The nitroimidazole group of drugs is remarkable in two respects [19] ... 

The utilization and activity (antimicrobial, antiprotozoan, antibacterial, anti-trichomonal, etc.) of other 2-nitroimidazole derivatives and also 4- and 5-nitroimidazoles are summarized in Table 3. The various activities of nitropyrazoles, nitrotriazoles, nitrotetrazoles, and nitrothiazoles are presented in Table 4. 

Special attention is paid to those nitroimidazole derivatives among which are medicines with a vividly expressed therapeutical activity (azomycine, metronidazole, ipronidazole, camidazole, dimetridazole, secnidazole, and many others) and to nitrotriazoles, nitrotetrazoles, and polynitroazoles used as high-energy compounds. 

Hypersensitivity to metronidazole, nitroimidazole derivatives, or any component of the formulation... 

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