Butoconazole nitrate Property

Melting point:

159°C (dec.)

storage temp. 

Sealed in dry,2-8°C

solubility 

DMSO or DMF: soluble

form 

powder

color 

White to Off-White

Merck 

14,1529

InChI

InChI=1S/C19H17Cl3N2S.HNO3/c20-15-7-4-14(5-8-15)6-9-16(12-24-11-10-23-13-24)25-19-17(21)2-1-3-18(19)22;2-1(3)4/h1-5,7-8,10-11,13,16H,6,9,12H2;(H,2,3,4)

InChIKey

ZHPWRQIPPNZNML-UHFFFAOYSA-N

SMILES

C(CN1C=NC=C1)(SC1C(Cl)=CC=CC=1Cl)CCC1=CC=C(Cl)C=C1.[N+]([O-])(=O)O

CAS DataBase Reference

64872-77-1(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

RTECS 

NI4399500

HS Code 

2933290000

Toxicity

LD50 in mice, male, female rats (mg/kg): >3200, >3200, 1720 orally; >1600, 940, 940 i.p. (Walker)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

Butoconazole nitrate Chemical Properties,Usage,Production

Description

Butoconazole Nitrate is the nitrate salt form of butaconazole, a synthetic imidazole derivative with fungistatic properties. Butoconazole is an imidazole antifungal agent that completely inhibits the growth of various fungi in vitro when used at concentrations of 0.05-30 μg/ml. It is active against vaginal infections of pure and mixed strains of C. albicans in mice when used vaginally at concentrations of 0.25-2% and 0.1-1%, respectively. Formulations containing butoconazole have been used in the treatment of vaginal yeast infections. Butoconazole Nitrate is an antifungal imidazole antimycotics. It is useful in the topical treatment of vulvovaginal candidiasis, being similar in effectiveness to miconazole and clotrimazole.

Chemical Properties

Butoconazole nitrate is a white to off-white crystalline powder with a molecular weight of 474.79. It is sparingly soluble in methanol, slightly soluble in chloroform, methylene chloride, acetone, and ethanol, very slightly soluble in ethyl acetate, and practically insoluble in water. It melts at about 159°C with decomposition.

Originator

Syntex (USA)

Uses

Imidazole derivative with antifungal properties

Definition

ChEBI: An organic nitrate salt obtained by reaction of equimolar amounts of butaconazole and nitric acid. An antifungal agent, it is used in gynaecology for treatment of vulvovaginal infections caused by Candida species, particularly Candida a bicans.

Application

Gynazole·1® contains 2% butoconazole nitrate (an imidazole derivative with antifungal activity) in cream of edetate disodium, glyceryl monostearate, methylparaben, mineral oil, polyglycerol-3 oleate, propylene glycol, propylparaben, colloidal silicon dioxide, sorbitol solution, purified water, and microcrystalline wax. Butoconazole nitrate is used locally in the treatment of vulvovaginal candidiasis. It is administered as a 100-mg suppository or 5 g (1 applicatorful) of a 2% cream for three consecutive nights.

Manufacturing Process

1H-Imidazole, 1-(4-(4-chlorophenyl)-2-((2,6-dichlorophenyl)thio)butyl)-, (+/- )-, mononitrate may be prepared by the same way as described below for enantiomers.
To a solution of Li2CuCl4 (0.10 M, 8.8 ml, 0.88 mmol) in dry THF (75 ml) was added dropwise a solution of 4-chloromagnesium chloride (17.5 mmol) in ether (15 ml) at -35°C. After stirring for 45 min, a pre-cooled (-35°C) solution of (S)-(+)-glycydil tosylate (2.0 g, 8.8 mmol) in THF (5 ml) was added via syringe. After 2 h at -35°C, the mixture was quenched with saturated NH4Cl and extracted with ether. The organic layer was dried (Na2SO4), evaporated to dryness and purificated by flash chromatography affording (2S)-1-(p-toluenesulphonyloxy)-4-(4-chlorophenyl)butan-2-ol, as a white solid (1.9 g, 77%), m.p. 72.7-74°C.
(2S)-1-[2-Hydroxy-4-(4-chlorophenyl)butyl]-1H-imidazole was prepared as follows: to a solution of imidasole (0.52 g, 7.61 mmol) in dry DMF (5 ml) at 0°C under N2 was added NaH (60% dispersion in oil, 0.3 g, 7.61 mmol). The reaction mixture was warmed to room temperature and stirred for 30 min. A solution of (2S)-1-(p-toluenesulphonyloxy)-4-(4chlorophenyl)butan-2-ol in DMF (15 ml) was then added dropwise over 15 min. The reaction mixture was heated at 75°C for 24 h, cooled poured into water and extracted with ethyl acetate. The organic phase was dried and evaporated and was the residue purified by flash chromatography. Gradient elution (1-5% MeOH/CH2Cl2) afforded (2S)-1-[2-hydroxy-4-(4-chlorophenyl)butyl]-1H-imidazole which was recrystallized from EtOAc/Et2O (236 mg, 67%), m.p. 128°-131°C; [α]D25- 23.23 (c 0.4, CHCl3).
(2S)-1-[2-Hydroxy-4-(4-chlorophenyl)butyl]-1H-imidazole nitrate was prepared as follows. To a solution of (2S)-1-(p-toluenesulphonyloxy)-4-(4- chlorophenyl)butan-2-ol (250 mg, 1 mmol) in THF (5 ml) at 0°C was added triethylamine (0.28 ml, 2.0 mmol), followed by methanesulfonyl chloride (0,15 ml, 2.0 mmol). The reaction mixture was was warmed to room temperature and stirred for 1 h. The mixture was poured into aq. NaHCO3, extracted with EtOAC, and the organic phase dried and evaporated to dryness. The resulting mesylate was dissolved in acetone (50 ml), then 2,6-dichlorobenzenethiol(464 mg, 2.6 mmol) and K2CO3 (568 mg, 4.1 mmol) were added. The mixture was heated at reflux under N2, cooled to room temperature, evaporated to dryness and partionated between water and EtOAc. The organic phase was dried (Na2SO4), evaporated, and residue purified by flash chromatography (1- 2% MeOH/CH2Cl2 gradient elution) to give an oil which was converted to nitrate salt. Recrystallization from EtOAc/Et2O gave 260 mg (55%) (2S)-1-[2- hydroxy-4-(4-chlorophenyl)butyl]-1H-imidazole nitrate, m.p. 120°-124°C; [α]D25+22.68 (c 0.4, EtOH).
The R enantiomer was prepared the same way from (-)-glycidyl tosylate.

brand name

Femstat (Roche);Femstat 3 (Bayer); Gynazole-1 (KV Pharmaceutical).

Therapeutic Function

Antifungal

Clinical Use

1-[4-(4-Chlorophenyl)-2-[(2,6-dichlorophenyl)-thio]butyl]-1H-imidazole (Femstat) is an extremely broad-spectrum antifungaldrug that is specifically effective against C. albicans.It is supplied as a vaginal cream containing 2% of thesalt. It is intended for the treatment of vaginal candidiasis.