Nitroimidazole

Last updated
5-Nitroimidazole [1]
4-Nitroimidazole.svg
Names
Preferred IUPAC name
5-Nitro-1H-imidazole
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.019.296 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 221-224-7
PubChem CID
UNII
  • InChI=1S/C3H3N3O2/c7-6(8)5-2-1-4-3-5/h1-3H Yes check.svgY
    Key: KUNMIWQQOPACSS-UHFFFAOYSA-N Yes check.svgY
  • c1cn(cn1)[N+](=O)[O-]
Properties
C3H3N3O2
Molar mass 113.076 g·mol−1
Melting point 303 °C (577 °F; 576 K) (decomposes)
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H302
P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Nitroimidazoles are the group of organic compounds consisting of an imidazole ring with at least one nitro group substituent. The term also refers to the class of antibiotics that have nitroimidazole in their structures. [2] These antibiotics commonly include the 5-nitroimidazole positional isomer.

Contents

Synthesis

Imidazole nitration.svg

Imidazole undergoes a nitration reaction with a mixture of nitric acid and sulfuric acid to give 5-nitroimidazole.

Nitroimidazole antibiotics

Position numbers on the ring Imidazole 2D numbered.svg
Position numbers on the ring

From the chemistry perspective, nitroimidazole antibiotics can be classified according to the location of the nitro functional group. Structures with names 4- and 5-nitroimidazole are equivalent from the perspective of drugs since these tautomers readily interconvert. Drugs of the 5-nitro variety include metronidazole, tinidazole, nimorazole, dimetridazole, pretomanid, ornidazole, megazol, and azanidazole. Drugs based on 2-nitroimidazoles include benznidazole and azomycin. [3]

Nitroimidazole antibiotics have been used to combat anaerobic bacterial and parasitic infections. [4] Perhaps the most common example is metronidazole. Other heterocycles such as nitrothiazoles (thiazole) are also used for this purpose. Nitroheterocycles may be reductively activated in hypoxic cells, and then undergo redox recycling or decompose to toxic products. [5]

Three nitroimidazole antibiotics: metronidazole, tinidazole, and nimorazole 5-Nitroimidazole antibiotics examples.svg
Three nitroimidazole antibiotics: metronidazole, tinidazole, and nimorazole

Related Research Articles

<span class="mw-page-title-main">Drug resistance</span> Pathogen resistance to medications

Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant.

<span class="mw-page-title-main">Metronidazole</span> Antibiotic and antiprotozoal medication

Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. It is an option for a first episode of mild-to-moderate Clostridioides difficile colitis if vancomycin or fidaxomicin is unavailable. Metronidazole is available orally, as a cream or gel, and by slow intravenous infusion.

<span class="mw-page-title-main">Imidazole</span> Chemical compound

Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non-adjacent nitrogen atoms in meta-substitution.

<span class="mw-page-title-main">Clavulanic acid</span> Molecule used to overcome antibiotic resistance in bacteria

Clavulanic acid is a β-lactam drug that functions as a mechanism-based β-lactamase inhibitor. While not effective by itself as an antibiotic, when combined with penicillin-group antibiotics, it can overcome antibiotic resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins.

<span class="mw-page-title-main">Daptomycin</span> Antibiotic

Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms.

<span class="mw-page-title-main">Tinidazole</span> Chemical compound

Tinidazole, sold under the brand name Tindamax among others, is a medication used against protozoan infections. It is widely known throughout Europe and the developing world as a treatment for a variety of anaerobic amoebic and bacterial infections. It was developed in 1972 and is a prominent member of the nitroimidazole antibiotic class.

<span class="mw-page-title-main">Ornidazole</span> Chemical compound

Ornidazole is an antibiotic used to treat protozoan infections. A synthetic nitroimidazole, it is commercially obtained from an acid-catalyzed reaction between 2-methyl-5-nitroimidazole and epichlorohydrin.

<span class="mw-page-title-main">Lincosamides</span> Group of antibiotics

Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.

<span class="mw-page-title-main">Platensimycin</span> Chemical compound

Platensimycin, a metabolite of Streptomyces platensis, is an antibiotic, which acts by blocking the enzymes β-ketoacyl-(acyl-carrier-protein ) synthase I/II (FabF/B).

<span class="mw-page-title-main">Benznidazole</span> Chemical compound

Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease, the effectiveness decreases in those who have long-term infection. It is the first-line treatment given its moderate side effects compared to nifurtimox. It is taken by mouth.

<span class="mw-page-title-main">Pretomanid</span> Chemical compound

Pretomanid is an antibiotic medication used for the treatment of multi-drug-resistant tuberculosis affecting the lungs. It is generally used together with bedaquiline and linezolid. It is taken by mouth.

β-Lactamase inhibitor Drugs that inhibit β-Lactamase enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

A nucleic acid inhibitor is a type of antibacterial that acts by inhibiting the production of nucleic acids. There are two major classes: DNA inhibitors and RNA inhibitors. The antifungal flucytosine acts in a similar manner.

<span class="mw-page-title-main">Solithromycin</span> Chemical compound

Solithromycin is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia and other infections.

<span class="mw-page-title-main">Quinolone antibiotic</span> Class of antibacterial drugs, subgroup of quinolones

Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry, specifically poultry production.

Cephalosporins are a broad class of bactericidal antibiotics that include the β-lactam ring and share a structural similarity and mechanism of action with other β-lactam antibiotics. The cephalosporins have the ability to kill bacteria by inhibiting essential steps in the bacterial cell wall synthesis which in the end results in osmotic lysis and death of the bacterial cell. Cephalosporins are widely used antibiotics because of their clinical efficiency and desirable safety profile.

<span class="mw-page-title-main">Ceftolozane/tazobactam</span> Antibiotic

Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a fixed-dose combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.

<span class="mw-page-title-main">2-Methylimidazole</span> Chemical compound

2-Methylimidazole is an organic compound that is structurally related to imidazole with the chemical formula CH3C3H2N2H. It is a white or colorless solid that is highly soluble in polar organic solvents and water. It is a precursor to a range of drugs and is a ligand in coordination chemistry.

<span class="mw-page-title-main">Disulfiram-like drug</span> Drug that causes an adverse reaction to alcohol

A disulfiram-like drug is a drug that causes an adverse reaction to alcohol leading to nausea, vomiting, flushing, dizziness, throbbing headache, chest and abdominal discomfort, and general hangover-like symptoms among others. These effects are caused by accumulation of acetaldehyde, a major but toxic metabolite of alcohol formed by the enzyme alcohol dehydrogenase. The reaction has been variously termed a disulfiram-like reaction, alcohol intolerance, and acetaldehyde syndrome.

Anti-ulcer agents are medications or supplements used to cure the damage of mucosal layer on organs to prevent the damage from further extending to deeper regions to cause complications.

References

  1. 4-Nitroimidazole at Sigma-Aldrich
  2. Edwards, David I. (1993). "Nitroimidazole drugs-action and resistance mechanisms I. Mechanism of action". Journal of Antimicrobial Chemotherapy. 31 (1): 9–20. doi:10.1093/jac/31.1.9. PMID   8444678.
  3. Jenks, Peter J. (2010-01-01), Finch, Roger G.; Greenwood, David; Norrby, S. Ragnar; Whitley, Richard J. (eds.), "CHAPTER 24 - Nitroimidazoles" , Antibiotic and Chemotherapy (Ninth Edition), London: W.B. Saunders, pp. 292–300, doi:10.1016/b978-0-7020-4064-1.00024-5, ISBN   978-0-7020-4064-1 , retrieved 2023-10-18
  4. Mital A (2009). "Synthetic Nitroimidazoles: Biological Activities and Mutagenicity Relationships". Sci Pharm. 77 (3): 497–520. doi: 10.3797/scipharm.0907-14 .
  5. Juchau, MR (1989). "Bioactivation in chemical teratogenesis". Annu. Rev. Pharmacol. Toxicol. 29: 165–167. doi:10.1146/annurev.pa.29.040189.001121. PMID   2658769.