443-48-1

Usage

InChI:InChI=1/C6H9N3O3/c1-5-7-6(9(11)12)4-8(5)2-3-10/h4,10H,2-3H2,1H3

Synthetic route

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

Conditions	Yield
With formic acid; sulfuric acid at 80℃; for 12h; Temperature;	88%
With formic acid at 50 - 60℃; for 0.5h; Reagent/catalyst; Temperature;	74.9%
With phosphoric acid; acetic anhydride In water at 25 - 30℃; for 2.5h; Yield given;
With sulfuric acid; acetic acid at 90℃; for 0.5h; Concentration; Temperature; Cooling;
With formic acid; sulfuric acid Large scale;

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

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	71%

metronidazole phosphate (73334-05-1) → metronidazole (443-48-1)

Conditions	Yield
With human serum In water at 37℃; human serum hydrolysis of metronidazole phosphate; pH dependence of solubility of metronidazole and metronidazole phosphate;

glycine ester of metronidaxole (89218-56-4) → metronidazole (443-48-1) + glycine (56-40-6)

Conditions	Yield
With aqueous buffer Rate constant; pHs 0.83-8.82, half-life times for the hydrolysis, also in simulated intestinal fluid (pH 7.55), Jones medium (pH 6.69) and Kupferberg medium (pH 6.11);

leucine ester of metronidaxole (98204-35-4) → L-leucine (61-90-5) + metronidazole (443-48-1)

Conditions	Yield
With aqueous buffer Rate constant; pHs 0.83-8.82, half-life times for the hydrolysis, also in simulated intestinal fluid (pH 7.55), Jones medium (pH 6.69) and Kupferberg medium (pH 6.11);

phenylalanine ester of metronidaxole (98204-36-5) → L-phenylalanine (63-91-2) + metronidazole (443-48-1)

Conditions	Yield
With aqueous buffer Rate constant; pHs 0.83-8.82, half-life times for the hydrolysis, also in simulated intestinal fluid (pH 7.55), Jones medium (pH 6.69) and Kupferberg medium (pH 6.11);

metronidazole glycyl glycinate hydrochloride (145615-34-5) → Glycine anhydride (106-57-0) + glycylglycine (556-50-3) + metronidazole (443-48-1)

Conditions	Yield
With aqueous buffer Rate constant; pHs 0.83-8.82, half-life times for the hydrolysis, also in simulated intestinal fluid (pH 7.55), Jones medium (pH 6.69) and Kupferberg medium (pH 6.11);

metronidazole glycyl phenylalaninate hydrochloride (145615-35-6) → Gly-Phe-OH (3321-03-7) + metronidazole (443-48-1) + cyclo(Gly-Phe) (5037-75-2, 10125-07-2, 23927-19-7)

Conditions	Yield
With aqueous buffer Rate constant; pHs 0.83-8.82, half-life times for the hydrolysis, also in simulated intestinal fluid (pH 7.55), Jones medium (pH 6.69) and Kupferberg medium (pH 6.11);

C6H9N3O3(1-) → metronidazole (443-48-1) + 2-(2-Methyl-5-nitroso-imidazol-1-yl)-ethanol

Conditions	Yield
In water at 20℃; under 735.5 Torr; Rate constant; also in the presence of enzymes or cellular extracts with nitroreductase, oxygen reductase, superoxide dismutase or nitrite raductase activity, variation of pH; also the radical anion of 5-nitro-2-furaldoxime;
In water at 20℃; under 735.5 Torr; Rate constant; also in the presence of a copper oxidase (laccase or ceruloplasmin); also the radical anion of misonidazole;

glycine ester of metronidaxole hydrochloride → metronidazole (443-48-1) + glycine (56-40-6)

Conditions	Yield
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;
With water at 37℃; Rate constant; rate constant of hydrolysis;

alanine ester of metronidaxole hydrochloride → L-alanin (56-41-7) + metronidazole (443-48-1)

Conditions	Yield
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;
With water at 37℃; Rate constant; rate constant of hydrolysis;

valine ester of metronidaxole hydrochloride → L-valine (72-18-4) + metronidazole (443-48-1)

Conditions	Yield
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;
With water at 37℃; Rate constant; rate constant of hydrolysis;

isoleucine ester of metronidaxole hydrochloride → L-isoleucine (73-32-5) + metronidazole (443-48-1)

Conditions	Yield
With water at 37℃; Rate constant; rate constant of hydrolysis;
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;

leucine ester of metronidaxole hydrochloride → L-leucine (61-90-5) + metronidazole (443-48-1)

Conditions	Yield
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;
With water at 37℃; Rate constant; rate constant of hydrolysis;

lysine ester of metronidaxole hydrochloride → L-lysine (56-87-1) + metronidazole (443-48-1)

Conditions	Yield
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;
With water at 37℃; Rate constant; rate constant of hydrolysis;

phenylalanine ester of metronidaxole hydrochloride → L-phenylalanine (63-91-2) + metronidazole (443-48-1)

Conditions	Yield
With sodium chloride at 25℃; Rate constant; rate constant of hydrolysis; pH 4.5; other pH, buffers;
With water at 37℃; Rate constant; rate constant of hydrolysis;

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

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Thermodynamic data; var. temp., ΔH(excit.), ΔS)(excit.);

2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-formylbenzoate → 4-Carboxybenzaldehyde (619-66-9) + metronidazole (443-48-1)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Thermodynamic data; var. temp., ΔH(excit.), ΔS)(excit.);

2-Formyl-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester (203124-48-5) → metronidazole (443-48-1) + o-carboxybenzaldehyde (119-67-5)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Mechanism;

3-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethoxy]-3H-isobenzofuran-1-one → metronidazole (443-48-1) + o-carboxybenzaldehyde (119-67-5)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Thermodynamic data; var. temp., ΔH(excit.), ΔS)(excit.);

2-Acetyl-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester → 2-acetyl-benzoic acid (577-56-0) + metronidazole (443-48-1)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Thermodynamic data; var. temp., ΔH(excit.), ΔS)(excit.);

2,6-Diformyl-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester → 2,6-diformylbenzoic acid (203124-57-6) + metronidazole (443-48-1)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant;

3-[2-(2-Methyl-5-nitro-imidazol-1-yl)-ethoxy]-1-oxo-1,3-dihydro-isobenzofuran-4-carbaldehyde → 2,6-diformylbenzoic acid (203124-57-6) + metronidazole (443-48-1)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Thermodynamic data; var. temp., ΔH(excit.), ΔS)(excit.);

2-(2,2,2-Trifluoro-acetyl)-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester → metronidazole (443-48-1) + 2-(2,2,2-trifluoroacetyl)benzoic acid (203124-56-5)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant; Thermodynamic data; var. temp., ΔH(excit.), ΔS)(excit.);

2-(2-Oxo-2-phenyl-acetyl)-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester → α,α'-dioxo-bibenzyl-2-carboxylic acid (3839-29-0) + metronidazole (443-48-1)

Conditions	Yield
With hydroxide In 1,4-dioxane; water at 30℃; Rate constant;

succinic acid bis-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl] ester (13357-09-0) → succinic acid (110-15-6) + metronidazole (443-48-1) + 4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy]-4-oxobutanoic acid (13182-87-1)

Conditions	Yield
With phosphate buffer pH 7.4 In methanol; water at 37℃; Rate constant; var. pH, also in human plasma, Wistar rat liver homogenate;

phthalic acid bis-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl] ester (206362-19-8) → benzene-1,2-dicarboxylic acid (88-99-3) + metronidazole (443-48-1) + 1,2-benzenedicarboxylic acid, mono[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]ester (126613-32-9)

Conditions	Yield
With phosphate buffer pH 7.4 In methanol; water at 37℃; Rate constant; var. pH, also in human plasma, Wistar rat liver homogenate;

Pentanedioic acid bis-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl] ester → 1,5-pentanedioic acid (110-94-1) + metronidazole (443-48-1) + 5-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy]-5-oxopentanoic acid

Conditions	Yield
With phosphate buffer pH 7.4 In methanol; water at 37℃; for 48h; Rate constant; Kinetics; var. pH, also in human plasma, Wistar rat liver homogenate;

Hexanedioic acid bis-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl] ester → Adipic acid (124-04-9) + metronidazole (443-48-1) + Hexanedioic acid mono-[2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl] ester

Conditions	Yield
With phosphate buffer pH 7.4 In methanol; water at 37℃; Rate constant; Kinetics; var. pH, also in human plasma, Wistar rat liver homogenate;

methanesulfonyl chloride (124-63-0) + metronidazole (443-48-1) → 2-(5-nitro-2-methyl-1-imidazolyl)ethyl methanesulfonate (30746-54-4)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃;	100%
With triethylamine In dichloromethane at 10 - 20℃; for 4h;	97%
With dmap; triethylamine In dichloromethane at 0 - 20℃;	97.5%

trifluoromethylsulfonic anhydride (358-23-6) + metronidazole (443-48-1) → 2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyl trifluoromethanesulfonate

Conditions	Yield
With dmap; triethylamine In dichloromethane at -10 - 20℃;	99.1%

metronidazole (443-48-1) → 1-(2-chloroethyl)-2-methyl-5-nitro-1H-imidazole (13182-81-5)

Conditions	Yield
With thionyl chloride at 0 - 50℃; for 2h;	99%
With thionyl chloride In dichloromethane at 20℃;	96%
With thionyl chloride for 3h; Heating;	90%

metronidazole (443-48-1) + trifluoroacetic acid (76-05-1) → C6H9N3O3*C2HF3O2

Conditions	Yield
In methanol at 65℃; for 0.25h;	99%

cadmium(II) acetate (543-90-8) + metronidazole (443-48-1) → C6H9N3O3*2C2H3O2(1-)*Cd(2+)

Conditions	Yield
In methanol at 20 - 40℃;	99%

zinc bis(2-methylphenoxyacetate) + metronidazole (443-48-1) → C6H9N3O3*2C9H9O3(1-)*Zn(2+)

Conditions	Yield
In methanol at 20 - 40℃;	99%

zinc bis(2-methylphenoxyacetate) + metronidazole (443-48-1) → 4C6H9N3O3*Zn(2+)*2C9H9O3(1-)

Conditions	Yield
In methanol at 20 - 40℃;	99%

2C9H9O3(1-)*Ca(2+) + metronidazole (443-48-1) → 2C6H9N3O3*Ca(2+)*2C9H9O3(1-)

Conditions	Yield
In methanol at 20 - 40℃;	99%

nickel diacetate (373-02-4, 14998-37-9, 33025-09-1, 94044-50-5, 98268-31-6) + metronidazole (443-48-1) → C6H9N3O3*2C2H3O2(1-)*Ni(2+)

Conditions	Yield
In methanol at 20 - 40℃;	99%

metronidazole (443-48-1) + Cysteamine (60-23-1) → 4-<(2-aminoethyl)thio>-2-methylimidazole-1-ethanol (78949-89-0)

Conditions	Yield
With pH 5.0 In water at 37℃; for 120h;	98%
With pH 5.0 at 37℃; for 120h; Product distribution; Mechanism; other reaction conditions;

metronidazole (443-48-1) → 1-(2-chloroethyl)-2-methyl-5-nitro-1H-imidazole hydrochloride

Conditions	Yield
With thionyl chloride In chloroform at 20℃; for 12h;	98%
With thionyl chloride In benzene for 2h; Heating;

metronidazole (443-48-1) + 1,1'-carbonyldiimidazole (530-62-1) → metronidazole imidazolide (877865-57-1)

Conditions	Yield
In chloroform at 20℃; Product distribution / selectivity;	98%
In dichloromethane at 20℃; Product distribution / selectivity;
In N,N-dimethyl-formamide for 12h;	7.32 g

zinc(II) 4-chlorophenylsulfanylacetate + metronidazole (443-48-1) → C6H9N3O3*2C8H6ClO2S(1-)*Zn(2+)

Conditions	Yield
In methanol at 20 - 40℃;	98%

Mn(2+)*2C8H7O4(1-) + metronidazole (443-48-1) → 2C6H9N3O3*Mn(2+)*2C8H7O4(1-)

Conditions	Yield
In methanol at 20 - 40℃;	98%

zinc diacetate (557-34-6) + metronidazole (443-48-1) → 2C6H9N3O3*2C2H3O2(1-)*Zn(2+)

Conditions	Yield
In methanol at 20 - 40℃;	98%

metronidazole (443-48-1) → 1-(2-fluoroethyl)-2-methyl-5-nitro-1H-imidazole

Conditions	Yield
With potassium fluoride; 1,3-bis(2,6-diisopropylphenyl)-2-fluoroimidazolium tetrafluoroborate In 1,4-dioxane at 40℃; for 17h; Inert atmosphere; Schlenk technique; Sealed tube;	98%
Stage #1: metronidazole With copper(l) chloride; diisopropyl-carbodiimide at 60℃; for 1h; Sealed tube; Microwave irradiation; Stage #2: With copper (II)-fluoride In water at 100℃; for 24h; Microwave irradiation;	61%

benzoyl chloride (98-88-4) + metronidazole (443-48-1) → 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl benzoate (13182-89-3)

Conditions	Yield
With dmap; ammonium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In chloroform at 5℃; for 3h; pH=9; Reagent/catalyst; Temperature; Solvent; pH-value;	97.38%
With pyridine In dichloromethane at 20℃;	85.12%
With triethylamine In 1,4-dioxane; chloroform 1.) r.t., 30 min, 2.) reflux, 4 h;

succinic acid anhydride (108-30-5) + metronidazole (443-48-1) → 4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy]-4-oxobutanoic acid (13182-87-1)

Conditions	Yield
With dmap In acetonitrile for 48h; Ambient temperature;	95%
With pyridine at 20℃; for 24h; Inert atmosphere; Cooling with ice;	95%
With sodium hydroxide In methanol; water at 60℃; for 2h;	94%

cis-Octadecenoic acid (112-80-1) + metronidazole (443-48-1) → 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl octadec-9-enoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃;	95%
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane for 4h; Esterification;	72%

potassium tetrachloroplatinate(II) (10025-99-7) + metronidazole (443-48-1) → cis-Pt(metronidazole)2Br2 (84431-30-1)

Conditions	Yield
With KBr In water 20-fold excess of KBr added to aq. soln. of K2(PtCl4), added solid ligand, stirred at 50 °C for 1 h; ppt. filtered, washed with EtOH/Et2O, Et2O, dried in vac.; elem. anal.;	95%

10-undecenoic acid (112-38-9) + metronidazole (443-48-1) → 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl undec-10-enoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃;	95%

metronidazole (443-48-1) + 4-cyano-N,N,N-trimethylanilinium trifluoromethansulfonate → 4-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzonitrile

Conditions	Yield
Stage #1: metronidazole With potassium hexamethylsilazane In tetrahydrofuran; N,N-dimethyl-formamide at 25℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 4-cyano-N,N,N-trimethylanilinium trifluoromethansulfonate In tetrahydrofuran; N,N-dimethyl-formamide at 25℃; for 3h; Inert atmosphere; Schlenk technique;	95%

pyridine{2-(2,2-bis(methoxycarbonyl)ethyl)-8-quinolinol-C,N,O}palladium(II) + metronidazole (443-48-1) → metronidazole{2-(2,2-bis(methoxycarbonyl)ethyl)-8-quinolinol-C,N,O}palladium(II)

Conditions	Yield
In benzene byproducts: pyridine; soln. of metronidazole (excess) and Pd compd. in benzene stirred for ca. 12 h at ca. 25 °C; evapn. in vac.; residue chromd. (TLC) on silica gel eluting with ethyl acetate;	94.8%

p-toluenesulfonyl chloride (98-59-9) + metronidazole (443-48-1) → toluene-4-sulfonic acid 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl ester (30575-42-9)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 5h;	94%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 3h;	90%
With pyridine	85%

(9R,12Z )-9-hydroxyoctadec-12-enoic acid (73891-08-4) + metronidazole (443-48-1) → 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 9-hydroxyoctadec-12-enoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃;	92%

potassium tetrachloroplatinate + metronidazole (443-48-1) → Pt(metronidazole)2I2 (85027-01-6, 84431-11-8)

Conditions	Yield
With potassium iodide In ethanol; water aq. soln. of KI was added to a soln. of Pt-complex in H2O, stirred for 1 min at room temp., a soln. of ligand in EtOH was added, stirred for 30min, stored at ca. 2°C overnight; elem. anal.;	91%

potassium tetrachloroplatinate(II) (10025-99-7) + metronidazole (443-48-1) → cis-Pt(metronidazole)2Cl2 (84151-71-3, 87037-14-7)

Conditions	Yield
In water 50°C, 1 h (crystn.); recrystn. (Me2CO/H2O);	91%
In water solid ligand added to aq. soln. of K2(PtCl4), stirred at 50 °C for 1 h; ppt. filtered, washed with EtOH/Et2O, Et2O, dried in vac.; elem. anal.;	90%

metronidazole (443-48-1) → 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (6058-57-7)

Conditions	Yield
With carbon tetrabromide; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 1.75h;	91%
With carbon tetrabromide; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 1.75h;	91%
With sulfuric acid; ammonium bromide In water at 120℃; for 12h;	87.6%
Stage #1: metronidazole With bromine; phosphorus trichloride In ethyl acetate for 3h; Reflux; Stage #2: With sodium hydroxide pH=5 - 6;

metronidazole (443-48-1) + m-Toluic acid (99-04-7) → 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 3-methylbenzoate (1403815-81-5)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	91%

phthalic anhydride (85-44-9) + metronidazole (443-48-1) → 1,2-benzenedicarboxylic acid, mono[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]ester (126613-32-9)

Conditions	Yield
With dmap In acetonitrile Ambient temperature;	90%
With dmap In acetonitrile at 20℃;	87.1%
With dmap In acetonitrile at 20℃;	87.1%
With dmap In acetonitrile

Upstream product

• 75-21-8 oxirane 
• 696-23-1 2-methyl-5-nitro-1H-imidazole 
• 73334-05-1 metronidazole phosphate 
• 89218-56-4 glycine ester of metronidaxole 
• 98204-35-4 leucine ester of metronidaxole 
• 98204-36-5 phenylalanine ester of metronidaxole 
• 145615-34-5 metronidazole glycyl glycinate hydrochloride 
• 145615-35-6 metronidazole glycyl phenylalaninate hydrochloride 
• 13182-89-3 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl benzoate 
• 203124-48-5 2-Formyl-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 

Downstream Products

• 30529-13-6 2-(4-[1,3]dioxolan-2-yl-styryl)-5-nitro-1-vinyl-1H-imidazole 
• 13182-87-1 4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy]-4-oxobutanoic acid 
• 104575-36-2 3,4,5-trimethoxy-benzoic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 
• 36698-08-5 1-(2-Benzoyloxyethyl)-5-nitro-2-imidazole-α-phenylethenol benzoate 
• 75787-17-6 C₂₇H₁₈Cl₃N₃O₆ 
• 75787-16-5 C₂₇H₁₈N₆O₁₂ 
• 131691-07-1 2-(2-methyl-5-nitroimidazole-1-yl)ethyl 4-bromophenylacetate 
• 104575-34-0 2-(2-methyl-5-nitroimidazol-1-yl)ethyl 3,4,5-triacetoxybenzoate 
• 131691-11-7 2-Phenyl-propionic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 
• 131691-08-2 3-Methyl-2-phenyl-butyric acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 
• 131691-05-9 (4-Acetoxy-phenyl)-acetic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 
• 131691-10-6 2-(4-Chloro-phenyl)-3-methyl-butyric acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 
• 131691-09-3 2-(4-Methoxy-phenyl)-3-methyl-butyric acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 
• 131691-12-8 2-(4-Chloro-phenyl)-propionic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester 

Relevant academic research and scientific papers

Method for synthesizing metronidazole under catalysis of solid acid

The invention discloses a method for synthesizing metronidazole under catalysis of solid acid. The method comprises the following steps that 2-methyl-5-nitroimidazole as a raw material and the solid acid as a catalyst react with ethylene oxide to obtain the metronidazole, wherein a reaction system is filtered to recycle the solid acid; a filtrate is concentrated and evenly mixed by adding water, and the pH value is adjusted to be 2-3 by adding alkali; the 2-methyl-5-nitroimidazole is recycled by filtration, the pH value of the filtrate is adjusted to be 10 again by adding alkali, and then themetronidazole can be obtained. The synthesizing process route is simple, the production cost is low, and the solid acid catalyst is environmentally friendly and can be recycled.

Synthetic method for producing metronidazole raw medicinal material

The invention discloses a synthetic method for producing a metronidazole raw medicinal material. The synthetic method comprises the following steps: (1) a synthetic reaction: putting reaction raw materials including 2.4 to 2.6 g of 2-methyl-5-nitroimidazole, 73 ml of absolute ethyl alcohol, 1.5 to 2 g of ethylene chlorohydrin and 4.5 to 5 g of K2CO3 into a reaction tank, raising the temperature to75 DEG C, preserving the temperature, controlling the temperature at 75 to 80 DEG C, reacting for 8 to 10 h, and stopping the reaction; and (2) carrying out immediate filtration in which a filter cake is byproduct potassium chloride, continuously evaporating a filter liquor to dryness, using methylene dichloride to dissolve at the temperature of 40 DEG C, cooling, separating out crystals, filtering, drying, and thus obtaining metronidazole. The method disclosed by the invention is mild in preparation condition and low in cost, and is applicable for industrial production.

Tritiated metronidazole and preparation method thereof

The invention belongs to the field of radioactive isotope labeling preparation, and particularly relates to tritiated metronidazole and a preparation method thereof. The preparation method includes: using 2-methyl-5-nitroimidazole as a raw material to react with N-iodosuccinimide to obtain 4-iodine-2-methyl-5nitroimidazole; under catalysis of palladium carbon, enabling 4-iodine-2-methyl-5nitroimidazole and tritium gas to be in tritium-halogen exchange to generate 4-3H-2-methyl-5-nitroimidazole; enabling 4-3H-2-methyl-5-nitroimidazole to react with ethylene oxide to obtain 4-3H-metronidazole. A synthetic product is purified through a prepared liquid phase to obtain4-3H-metronidazole with high specific activity (22.08Ci/g), high radiochemical purity (greater than or equal to 98%) and high chemical purity (greater than or equal to 98%). The tritiated metronidazole can be used as a radioactive tracer in studying absorption, distribution, metabolism and residue elimination of metronidazole in animal bodies.

Environment-friendly method for metronidazole synthesis

The invention discloses an environment-friendly method for metronidazole synthesis. Formic acid is replaced with acetic acid, alcohol is added for esterification, neutralization is performed for three times, sodium sulfate and ethylene glycol are recovered, a nitration product is effectively recovered from a metronidazole mother solution, derivatives such as acetic ester, anhydrous sodium sulfate and the like are obtained, by-products such as ethylene glycol and the like are chemical raw materials with wide applications, resources are recycled, the raw materials are greatly saved, the production cost is reduced, and the whole novel process adopts simple steps and is convenient to operate.

Metronidazule raw materials method for producing synthetic cleaning

The invention relates to a clean production method for synthesizing metronidazole, and belongs to the field of the organic synthesis of drugs. The method comprises the following steps: 1, utilizing a neutralizing second mother liquor (with the pH value of 10.5-11.0) in a metronidazole synthesis process to substitute a 30% sodium hydroxide solution to be used in a neutralization reaction of a metronidazole hydroxylation liquid; and 2, carrying out concentrated recovery on the above finally obtained metronidazole production mother liquor before emission, neutralizing the mother liquor by sulfuric acid until the pH value is 5.0-6.0, allowing the neutralized solution to stand for above 6h, centrifuging to obtain a nitro substance, and sending the recovered mother liquor to a sewage treatment station. About 200kg of the 30% sodium hydroxide solution is saved each batch, the emission of the neutralizing second mother liquor (with the pH value of 10.5-11.0) is reduced, cycle production is formed, the environmental protection throughput is reduced, and the production cost is reduced. The wet product of the recovered nitro substance in each batch is about 18kg, so the production cost is reduced, and the environmental protection throughout is reduced.

Metronidazole esters: A new class of antiglycation agents

A series of metronidazole ester derivatives 1-34 has been synthesized with the aim of developing new leads with antiglycation activity. The in vitro evaluation of antiglycation potential of 1-34 showed that the ester derivatives 28, 16, and 3 have IC50 values 218.97 ± 2.5, 245.3 ± 5.1, and 278.6 ± 0.8 μM, respectively, comparable to the standard agent, rutin (IC50 = 294.5 ± 1.50 μM). The study identifies a new class of potent antiglycation agents. A structure-activity relationship has also been evaluated. All the compounds were characterized by using spectroscopic techniques, including 1H NMR, IR, and EI-MS.

External preparation for skin diseases containing nitroimidazole

An external preparation for skin disease which comprises a nitroimidazole derivative represented by the following formula (I): wherein R1, R3 and R4 may be the same or different and represent a hydrogen atom, a nitro group, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, or a substituted lower alkenyl group; and R2 represents a hydrogen atom, a lower alkyl group, a substituted lower alkyl group and a lower alkenyl group or a substituted lower alkenyl group, provided that any one of R1, R3 and R4 is a nitro group.

Gel compositions containing metronidazole

An aqueous solution of metronidazole in which the concentration of metronidazole is higher than 0.75%. The solution contains the solubility enhancer hydroxypropyl-betacyclodextrin and may additionally contain niacinamide. Methods of manufacture and therapeutic use of the solution are disclosed.

Chemical compounds having ion channel blocking activity for the treatment of immune dysfunction

The present invention relates to chemical compounds having inhibitory activity on an intermediate conductance Ca 2+ activated potassium channel (IK Ca), and the use of such compounds for the treatment or alleviation of diseases or conditions relating to immune dysfunction. Moreover, the invention relates to a method of screening a chemical compound for inhibitory activity on an intermediate conductance Ca 2+ activated potassium channel (IK Ca).

Synthesis, chemical and enzymatic hydrolysis, and bioavailability evaluation in rabbits of metronidazole amino acid ester prodrugs with enhanced water solubility

A series of amino acid esters (3a-e) have been synthesized and evaluated as potential prodrugs of metronidazole with the aim of improving aqueous solubility and therapeutic efficacy. The aqueous solubility and the lipophilicity (expressed as the log P value) of metronidazole and its esters were investigated. In general the prodrugs revealed enhanced water solubility compared with metronidazole. N,N-diethylglycinate hydrochloride (3a) and 4-ethylpiperazinoacetate (3e) derivatives displayed higher aqueous solubility, which exceeded that of the parent drug by factors of approximately 140 and 100, respectively. All the esters revealed lower log P values than metronidazole except for the 4-phenylpiperazinoacetate derivative (3f), which was 6.5-times more lipophilic than metronidazole. The hydrolysis kinetics of the esters were studied in aqueous phosphate buffer (pH 7.4) and 80% human plasma at 37°C. In all cases the hydrolysis followed pseudo-first-order kinetics and resulted in a quantitative reversion to metronidazole as evidenced by HPLC analysis. The prodrugs exhibited adequate chemical stability (half-life, t1/2, 4-16 h) in aqueous phosphate solution of pH 7.4. In 80% human plasma they were hydrolysed within a few minutes to metronidazole. The esters 3d (methylpiperazinoacetate derivative) and 3f were exempted since their t1/2 values were approximately 2.5 and 8.5 h, respectively. A comparative pH-rate profile study of N,N-diethylglycinate hydrochloride (3a) and 4-ethylpiperazinoacetate (3e) derivatives in aqueous buffer solution over the pH range 2.2-10 was investigated. The results indicated that 3a showed marked stability at pH 2-6 followed by accelerated hydrolysis at pH 7.4. The basic ester 3e was found to be less stable at lower pH values but exhibited comparative stability at physiological pH. Moreover, in-vivo experiments in rabbits revealed a higher metronidazole plasma level with sustained release characteristics within the prodrug-treated animals (10- and 2.5-fold) as compared with the parent drug-treated group. In conclusion, the designed amino acid esters 3a and 3c-e might be considered as good candidates for water-soluble prodrug forms of metronidazole.