Butoconazole

Description

Butoconazole is an imidazole that is pharmacologically quite comparable to clotrimazole. It is a vaginal antifungal agent that increases cell membrane permeability in susceptible fungi. It is indicated for local treatment of vulvovaginal candidiasis (moniliasis).

Uses

Butoconazole is a fungostatic drug, and it is formally classified as an imidazole, but only because of the presence of an imidazole ring in the structure. It is believed that butoconazole, like miconazole, econazole, and other “pure” representatives of the imidazole class, also inhibits the biosynthesis of estrosterin in the cytoplasmatic membrane of fungi; however, it is very possible that this is not the only mechanism of its action. It is effective for vaginal infections caused by various types of candida. It is also used only externally and vaginally. Synonyms of this drug are femstat, listomin, and others.

Uses

antineoplastic, pyrimidine antimetabolite

Definition

ChEBI: A member of the class of imidazoles that is 1H-imidazole in which the hydrogen attached to the nitrogen is substituted by a 4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)sulfanyl]butyl group. An antifungal agent, it is used as its nitrate sa t in gynaecology for treatment of vulvovaginal infections caused by Candida species, particularly Candida albicans.

Indications

Butoconazole is generally indicated for therapy of vulvovaginal mycoses caused by Candida species and Candida (Torulopsis) glabrata.

brand name

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

Antimicrobial activity

Broad-spectrum imidazole antimycotic with in vitro and in vivo activitiy against pathogenic yeasts, dermatophytes, moulds, and dimorphic fungi.

Side effects

Local irritations such as itching and burning sensations and allergic reactions may occur in rare cases and are mainly due to the galenic formulation.

Synthesis

Butoconazole, 1-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)thio]butyl]- 1H-imidazole (35.2.12), is synthesized from 4-chlorobenzylmagnesium bromide, which is reacted with epichloridrine to make 4-(4
-chlorophenyl)-1-chlorobutan-2-ol (35.2.10), which is reacted with imidazole in the presence of sodium to make 4-(4-chlorophenyl)- 1-(1H-imidazolyl)butanol-2 (35.2.11). The hydroxyl group in the last is replaced with a chlorine atom upon reaction with thionyl chloride, which is then by the reaction with 2,6- dichlorothiophenol butoconazole, is obtained.

Enzyme inhibitor

This fungicide (FW = 411.78 g/mol; CAS 64872-77-1), also known as Femstat?, Femstat-3?, Gynazole-1?, and systematically as 1-[4- (4- chlorophenyl) -2-[ (2,6-dichlorophenyl) -sulfanyl]butyl]-1H-imidazole (* = chiral center), is believed to inhibit steroid synthesis, targeting the conversion of lanosterol to ergosterol and modifying membrane composition/function. At 80 μM, butoconazole was strictly fungistatic against early stationary-phase Candida albicans cells. During early log- phase growth, butoconazole were highly lethal at 20 μM. In 1995, butoconazole was approved for treatment of vaginal yeast infections.

Raw materials

Preparation Products