Chemical Properties
White Solid
Uses
antifungal for cutaneous infections
Uses
Tolnaftate topical is used to treat skin infections such as athlete's foot, jock itch, and ringworm infections. Tolnaftate is also used, along with other antifungals, to treat infections of the nails, scalp, palms, and soles of the feet. The powder and po
Definition
ChEBI: A monothiocarbamic ester that is the methyl(3-tolyl)carbamothioate ester of 2-naphthol. A synthetic anti-fungal agent used to treat jock itch, athlete's foot and ringworm.
General Description
Crystals or white powder.
Air & Water Reactions
Thio and dithiocarbamates slowly decompose in aqueous solution to form carbon disulfide and methylamine or other amines. Such decompositions are accelerated by acids. Insoluble in water.
Reactivity Profile
Tolnaftate is a thiocarbamate. Flammable gases are generated by the combination of thiocarbamates and dithiocarbamates with aldehydes, nitrides, and hydrides. Thiocarbamates and dithiocarbamates are incompatible with acids, peroxides, and acid halides.
Health Hazard
SYMPTOMS: In susceptible persons, Tolnaftate may cause sensitization or irritation.
Fire Hazard
Flash point data on Tolnaftate are not available, Tolnaftate is probably combustible.
Description
Tolnaftate is a thiocarbamate antifungal agent.
1 It is active against clinical isolates of the dermatophytes
T. rubrum,
T. mentagraphytes,
T. verrucosum,
E. floccosum, and
M. canis (MIC
50s = 50, 100, 6, 50, and 50 ng/ml, respectively), as well as 18 additional yeast and filamentous fungi species (MIC = 0.003-0.8 μg/ml).
2,
3 Tolnaftate also reduces aflatoxin production in
A. parasiticus in a concentration-dependent manner.
4 It inhibits squalene epoxidase with an IC
50 value of 12.5 μg/ml in a cell-free assay.
1
Originator
Tinactin,Schering,US,1965
Indications
Tolnaftate (Aftate, Tinactin, etc.) is an odorless and nonstaining synthetic
antifungal agent whose exact mechanism of action is unknown. It is effective
against dermatophytes and P. orbiculare and Pityrosporum ovale. It is
ineffective against C. albicans and bacteria.
Manufacturing Process
In a first step, 2-naphthol is reacted with thiophosgene to give 2-naphthyl
chlorothionoformate.
A mixture of 4.0 grams of N-methyl-3-toluidine and 2.8 grams of sodium
hydrogencarbonate in 50 cc of acetone was stirred at 0° to 10°C and 7.4 grams of 2-naphthyl chlorothionoformate was added in small portions thereto
and the mixture was heated under reflux for 30 minutes. The cooled mixture
was poured into about 150 cc of cold water and 2-naphthyl-N-methyl-N-(3-
tolyl)thionocarbamate was obtained as white crystals. Yield is 9.1 grams
(90%). Recrystallization from alcohol gave colorless needle crystals, MP
110.5° to 111.5°C.
Therapeutic Function
Antifungal
Clinical Use
O,2-Naphthyl m,N-dimethylthiocarbanilate (Tinactin,Aftate, NP-27) is a white crystalline solid that is insoluble inwater, sparingly soluble in alcohol, and soluble in most organicsolvents. The compound, a thioester of β-naphthol, isfungicidal against dermatophytes, such as Trichophyton,Microsporum, and Epidermophyton spp., that cause superficialtinea infections. Tolnaftate is available in a concentrationof 1% in creams, powders, aerosols, gels, and solutionsfor the treatment of ringworm, jock itch, and athlete’s foot.Tolnaftate has been shown to act as an inhibitor of squaleneepoxidase in susceptible fungi, so it is classified with theallylamine antimycotics. Tolnaftate is formulated into preparationsintended to be used with artificial fingernails to counteractthe increased chance of ringworm of the nail beds.
Clinical Use
Tolnaftate (Tinactin, others) is a nonprescription antifungal
agent effective in the topical treatment of dermatophyte
infections and tinea. The mechanism of action
is unknown.
Synthesis
Tolnaftate, O-(2-naphthyl)-N-methyl-N-(3-tolyl)-thiocarbamate (35.4.9), is synthesized by reacting equimolar amounts of 2-naphthol and thiophosgene to make a monosubstituted product of thiophosgene (35.4.8), which is then reacted with N-methyl-3-toluidine to
give the desired tolnaftate.
