6506-37-2

Basic information

• Product Name: Nimorazole
• Synonyms: 1-(2-N-Morpholinylethyl)-5-nitroimidazole;Acterol;Acterol forte;Esclama;Morpholine, 4-[2-(5-nitro-1H-imidazol-1-yl)ethyl]-;Morpholine, 4-[2-(5-nitroimidazol-1-yl)ethyl]-;Nimorazole 4-[2-(5-Nitroimidazol-1-yl)ethyl]morpholine;Nimorazole, 6506-37-2
• CAS NO: 6506-37-2
• Molecular Formula: C₉H₁₄N₄O₃
• Molecular Weight: 226.23
• EINECS: 229-394-4
• Product Categories: API;Inhibitors
• Mol File: 6506-37-2.mol
• Article Data: 2

Chemical Properties

• Melting Point: 110-111°
• Boiling Point: 367.84°C (rough estimate)
• Flash Point: 221.7°C
• Appearance: /
• Density: 1.2673 (rough estimate)
• Vapor Pressure: 4.8E-08mmHg at 25°C
• Refractive Index: 1.6300 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 6.65±0.10(Predicted)
• CAS DataBase Reference: Nimorazole(CAS DataBase Reference)
• NIST Chemistry Reference: Nimorazole(6506-37-2)
• EPA Substance Registry System: Nimorazole(6506-37-2)

Safety Data

• Hazardous Substances Data: 6506-37-2(Hazardous Substances Data)

Usage

Description

Nimorazole is 5-nitroimidazole with antimicrobial and radiosensitizing activities. It is active against T. vaginalis in a Coulter counter antimicrobial assay (EC50 = 2.55 fmol/cell) and G. intestinalis (IC50 = 0.393 μM). Nimorazole reduces the number of vaginal trichomonads in a mouse model of T. vaginalis intravaginal infection (ED50 = 5.62 mg/kg). Under hypoxic conditions, nimorazole enhances radiation-induced SCC-7 tumor cell death in vitro and in vivo.

Originator

Naxogin,Carlo Erba,UK,1970

Uses

Nimorazole is an antimicrobial with activity against anaerobic bacteria and protozoa.

Manufacturing Process

6 g 4(5)-nitroimidazole sodium salt and 9 g β-chloroethylmorpholine are allowed to react in 200 ml dry toluene. The mixture is refluxed for 50 hours, then cooled and filtered from the solid residue. The solvent is evaporated under reduced pressure. The half-solid product thus obtained solidifies by addition of petroleum ether and ethyl ether.Crystallization from water results in N-β-ethylmorpholino-(5)-nitroimidazole (melting point 110°C to 111°C); from mother liquors N-β-ethylmorpholino- (4)-nitroimidazole (melting point 104°C to 106°C) is obtained.The following procedure is given in US Patent 3,458,528: 78 grams (0.675 mol) of 5-nitroimidazole is dissolved in 1,500 ml of acetic acid upon the addition of 72 ml (0.57 mol) of boron trifluoride etherate. 175 ml (3.5 mols) of ethylene oxide in 175 ml of hexane, in a dropping funnel topped with a cold finger, is added slowly over 1 hour to the above solution maintained at 32° to 35°C with a water cooling bath. The mixture is concentrated under high vacuum to 100 to 150 ml volume. The residue is diluted with 500 ml of water, neutralized to pH 7 with aqueous sodium hydroxide, and extracted with 1.5 liters of ethyl acetate. The extract is dried and evaporated to yield 1-(2'- hydroxyethyl)-5-nitroimidazole.20 grams (0.127 mols) of 1-(2'-hydroxyethyl)-5-nitroimidazole in 50 ml of dry pyridine is reacted with 75 grams of p-toluenesulfonyl chloride at 15°C for 4 hours. The reaction mixture is poured into ice and water and the crystalline precipitate is separated by filtration, washed with water and air dried to yield 1-(2'-p-toluenesulfonyloxyethyl)-5-nitroimidazole; MP 126° to 127°C.16 grams, (0.057 mol) of 1-(2'-p-toluenesulfonyloxyethyl)-5-nitroimidazole and 9.3 ml of morpholine are heated at 95°C for 4 hours. The reaction mixture is taken up in water and extracted with ether. Evaporation of the ether yields 1-(2'-N-morpholinylethyl)-5-nitroimidazole; MP 109° to 110°C.

Therapeutic Function

Trichomonacidal

Pharmaceutical Applications

An orally administered 5-nitroimidazole. It is slightly soluble in water at room temperature, soluble in alcohols, acetone and chloroform. The spectrum includes T. vaginalis, G. lamblia, E. histolytica, anaerobic bacteria and G. vaginalis. Activity against B. fragilis and Fusobacterium spp. is similar to or slightly less than that of metronidazole (mean MIC 0.25–1 mg/L).A peak blood concentration of about 32 mg/L occurs within 2 h of a 500 mg oral dose. High concentrations are achieved in saliva and vaginal secretions. Excretion is principally via the urine where the drug appears as metabolites which display antimicrobial and antiprotozoal activity less than that of the parent drug.It is generally well tolerated even at the high doses required in conjunction with radiotherapy for the treatment of head and neck tumors. Adverse effects are the same as those of metronidazole. Disulfiram-like reactions appear to be rare.Clinical uses are similar to those of metronidazole. It is also used as a hypoxic radiosensitizer in the radiotherapy of head and neck tumors.

InChI:InChI=1/C9H14N4O3/c14-13(15)9-7-10-8-12(9)2-1-11-3-5-16-6-4-11/h7-8H,1-6H2

Synthetic route

potassium tetrachloroplatinate(II) (10025-99-7) + nimorazole (6506-37-2) → (NO2CCHNCHN(CH2CH2NCH2CH2OCH2CH2))2PtCl2 (84431-24-3)

Conditions	Yield
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.;	70%

Relevant articles and documents

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.