Metronidazole

Base Information

• Chemical Name: Metronidazole
• CAS No.: 443-48-1
• Molecular Formula: C6H9N3O3
• Molecular Weight: 171.156
• Hs Code.: 29332990
• European Community (EC) Number: 207-136-1
• NSC Number: 757118,69587,50364
• UNII: 140QMO216E
• DSSTox Substance ID: DTXSID2020892
• Nikkaji Number: J2.046J
• Wikipedia: Metronidazole
• Wikidata: Q169569
• NCI Thesaurus Code: C651
• RXCUI: 6922
• Metabolomics Workbench ID: 43184
• ChEMBL ID: CHEMBL137
• Mol file: 443-48-1.mol

Synonyms:2 Methyl 5 nitroimidazole 1 ethanol;2-Methyl-5-nitroimidazole-1-ethanol;Bayer 5360;Clont;Danizol;Flagyl;Gineflavir;Metric;Metrodzhil;MetroGel;Metrogyl;Metronidazole;Metronidazole Hydrochloride;Metronidazole Monohydrochloride;Metronidazole Phosphate;Metronidazole Phosphoester;Satric;Trichazol;Trichopol;Trivazol;Vagilen

Chemical Property of Metronidazole

Chemical Property:

• Appearance/Colour: white to slightly yellow crystalline powder
• Vapor Pressure: 2.67E-07mmHg at 25°C
• Melting Point: 159-161 °C(lit.)
• Refractive Index: 1.612
• Boiling Point: 405.4 °C at 760 mmHg
• PKA: pKa 2.62(H2O,t =25±0.2,Iundefined) (Uncertain)
• Flash Point: 199 °C
• PSA: 83.87000
• Density: 1.45 g/cm³
• LogP: 0.61520
• Storage Temp.: 2-8°C
• Solubility.: acetic acid: 0.1 M, clear, faintly yellow
• Water Solubility.: <0.1 g/100 mL at 20℃
• XLogP3: 0
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 171.06439116
• Heavy Atom Count: 12
• Complexity: 170

Purity/Quality:

Above 99% ^*data from raw suppliers

Metronidazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, T
• Hazard Codes: Xn,T,F
• Statements: 40-46-45-39/23/24/25-23/24/25-11
• Safety Statements: 36/37-45-53-16-7

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CC1=NC=C(N1CCO)[N+](=O)[O-]
• Recent ClinicalTrials: Surgical Access Combined With Systematically Administered Antibiotics in the Treatment of Peri-implantitis
• Recent EU Clinical Trials: Evaluation of the efficacy of treatment with mucosal bacterial vaccines (autovaccines) versus suppressive antibiotic treatment in subjects with hip or knee prosthesis infections.
• Recent NIPH Clinical Trials: Study to Assess Efficacy and Safety of PF-06947386 in Japanese Adult Patients With Complicated Intra-abdominal Infection
• Indications: Against infections caused by Trichomonas vaginalis, Entamoeba histolytica (acute intestinal type and liver abscesses), Giardia lamblia and Dracunculus medinensis. During treatment of trichomoniasis it is wise to treat the male partner as well. In amoebiasis, a luminal amoebicide is added to eliminate surviving organisms in the colon. Metronidazole is also used for the treatment of infections due to anaerobic bacteria. Metronidazole (Flagyl, Metrogel) exerts activity against most anaerobic bacteria and several protozoa.The drug freely penetrates protozoal and bacterial cells but not mammalian cells. Metronidazole can function as an electron sink, and because it does so, its 5-nitro group is reduced. The enzyme, pyruvate-ferredoxin oxidoreductase, found only in anaerobic organisms, reduces metronidazole and thereby activates the drug. Reduced metronidazole disrupts replication and transcription and inhibits DNA repair.
• Description: Metronidazole is a nitroimidazole antibiotic first isolated in the 1950s. Many nitroimidazoles were being studied at the time, as the class was found to have trichomonacidal properties. Metronidazole was of particular interest due to its high activity against Trichomonas vaginalis and Entamoeba histolytica both in vitro and in vivo as well as clinical activity against many anaerobic pathogens including Gram-positive and Gramnegative bacteria and Giardia lamblia. Metronidazole is often used clinically for intra-abdominal infections and is the firstline treatment for Clostridium difficile–associated diarrhea.
• Uses: Metronidazole is the drug of choice for amebiases, vaginal trichomonasis and trichlomonadic urethritis in men, lambliosis, amebic dysentery, and anaerobic infections caused by microorganisms that are sensitive to the drug. Synonyms of this drug are flagyl, protostat, trichopol, and vagimid. Metronidazole is available as oral, intravaginal, topical, and parenteral preparations. It is manufactured by several companies, but is only available by prescription. Unintentional environmental exposure is unlikely, and if it occurs, it is very unlikely to cause toxicity. Used as an antibacterial in the treatment of rosacea. Antiprotozoal (trichomonas). A potential human carcinogen. Metronidazole, is an antibiotic and antiprotozoal agent. It is mainly used to treat or prevent systemic or local infections caused by anaerobic bacteria, such as anaerobic bacterial infections in the abdominal cavity, digestive tract, female reproductive system, lower respiratory tract, skin and soft tissues, bones and joints, etc. Inflammation, meningeal infections, and colitis caused by antibiotic use are also effective. Tetanus is often treated with tetanus antitoxin (TAT). It can also be used for oral anaerobic infection. On October 27, 2017, the list of carcinogens published by the World Health Organization's International Agency for Research on Cancer was preliminarily sorted for reference, and metronidazole was included in the list of class 2B carcinogens. In January 2020, metronidazole was selected into the second batch of national centralized drug procurement list.
• Therapeutic Function: Antiprotozoal
• Clinical Use: Metronidazole is the most effective agent available for the treatment of individuals with all forms of amebiasis, with perhaps the exception of the person who is asymptomatic but continues to excrete cysts. That situation calls for an effective intraluminal amebicide, such as diloxanide furoate, paromomycin sulfate, or diiodohydroxyquin. Metronidazole is active against intestinal and extraintestinal cysts and trophozoites. Although quinacrine hydrochloride has been used for the treatment of giardiasis, many physicians prefer metronidazole. Furazolidone is an alternate choice. Metronidazole is the drug of choice in Europe for anaerobic bacterial infections; concern about possible carcinogenicity has led to some caution in its use in the United States.Recently it has been found to be effective in treating D. medinensis (Guinea worm) infections and Helicobacter pylori.
• Drug interactions: Potentially hazardous interactions with other drugs Alcohol: disulfiram-like reaction. Anticoagulants: effects of coumarins enhanced. Antiepileptics: metabolism of phenytoin inhibited; concentration reduced by phenobarbital. Busulfan: concentration of busulfan increased - risk of toxicity. Ciclosporin: raised blood level of ciclosporin. Cytotoxics: busulfan concentration increased; metabolism of fluorouracil inhibited.

Technology Process of Metronidazole

There total 47 articles about Metronidazole which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 88.0%

oxirane (75-21-8,99932-75-9) + 2-methyl-5-nitro-1H-imidazole (696-23-1,88054-22-2) → metronidazole (443-48-1)

Guidance literature:

With formic acid; sulfuric acid; at 80 ℃; for 12h; Temperature;

Reference yield: 71.0%

2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl benzoate (13182-89-3) + benzoic acid (65-85-0,8013-63-6) → metronidazole (443-48-1)

Guidance literature:

With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20 ℃;

DOI:10.2174/157340612802084360

Reference yield:

metronidazole palmitate (13182-85-9) → 1-hexadecylcarboxylic acid (57-10-3) + metronidazole (443-48-1)

Guidance literature:

With hydrogenchloride; citrate-phosphate-borate buffer; In ethanol; at 60 ℃; pH=3; Further Variations:; pH-values; Kinetics;

upstream raw materials:

oxirane

2-methyl-5-nitro-1H-imidazole

metronidazole phosphate

glycine ester of metronidaxole

Downstream raw materials:

3,4,5-trimethoxy-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester

C₂₇H₁₈Cl₃N₃O₆

4-[2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethoxy]benzaldehyde

1-(2-bromoethyl)-2-methyl-5-nitroimidazole

Refernces

• 1、 Ayscough et al.. "-". . . Retrieved 1978.
• 2、 -. "Synthetic method for producing metronidazole raw medicinal material". Paragraph 0013-0014. . Retrieved 2018/07/30.
• 3、 -. "Environment-friendly method for metronidazole synthesis". Paragraph 0040; 0041; 0047; 0048. . Retrieved 2016/10/07.