N-methyl-N-(3-methylphenyl)-1-(naphthalen-2-yloxy)methanethioamide

• ChemBase ID: 407
• Molecular Formular: C19H17NOS
• Molecular Mass: 307.40938
• Monoisotopic Mass: 307.10308517
• SMILES: S=C(Oc1cc2c(cc1)cccc2)N(c1cc(ccc1)C)C
• Canonical SMILES: Cc1cccc(c1)N(C(=S)Oc1ccc2c(c1)cccc2)C
• InChI: InChI=1S/C19H17NOS/c1-14-6-5-9-17(12-14)20(2)19(22)21-18-11-10-15-7-3-4-8-16(15)13-18/h3-13H,1-2H3
• InChIKey: FUSNMLFNXJSCDI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-methyl-N-(3-methylphenyl)-1-(naphthalen-2-yloxy)methanethioamide
• IUPAC Traditional name: tolnaftate
• Brand Name: Chinofungin; Dr. Scholl's athlete's foot spray; Dermoxin; Dungistop; Focusan; Fungistop; Genaspore cream; Hi-alarzin; Hi-alazin; NP-27 Cream; NP-27 Powder; NP-27 Solution; NP-27 Spray Powder; Naphthiomate T; Naphthiomate-t; O-2-Naphthyl N,N-dimethylthiocarbanilate; O-2-Naphthyl M,N-dimethylthiocarbanilate; Phytoderm; Pitrex; Pitrex cream; Prestwick_472; Separin; Separin (TN); Sorgoa; Sporiline; Timoped; Tinactin; Tinactin (TN); Tinactin aerosol liquid; Tinactin aerosol powder; Tinactin antifungal deodorant powder aerosol; Tinactin cream; Tinactin jock itch aerosol powder; Tinactin jock itch cream; Tinactin jock itch spray powder; Tinactin plus aerosol powder; Tinactin plus powder; Tinactin powder; Tinactin solution; Tinaderm; Tinavet; Tinavet (veterinary); Ting antifungal cream; Ting antifungal powder; Ting antifungal spray liquid; Ting antifungal spray powder; Ting products; Tniaderm; Tolnaftate (JP14/USP); Tolnaftate (JP15/USP); Tolnaftate [usan:ban:inn:jan]; Tolnaftate(USAN); Tolnaftato [DCIT]; Tolnaftato [inn-spanish]; Tolnaftatum [inn-latin]; Tolnaphthate; Tolsanil; Tonoftal; Tritin; Zeasorb-AF; Zeasorb-AF powder; M,N-Dimethylthiocarbanilic acid O-2-naphthyl ester; o-(2-Naphthyl) methyl(3-methylphenyl)thiocarbamate; 2-Naphthyl N-methyl-N-(3-tolyl)thionocarbamate; Aftate; Aftate for athlete's foot aerosol spray liquid; Aftate for athlete's foot aerosol spray powder; Aftate for athlete's foot gel; Aftate for athlete's foot sprinkle powder; Aftate for jock itch aerosol spray powder; Aftate for jock itch gel; Aftate for jock itch sprinkle powder; Carbanilic acid, N,M-dimethylthio-, O-2-naphthyl ester; Carbanilic acid, M,N-dimethylthio-, O-2-naphthyl ester
• Synonyms: Tolnaftate; O-2-Naphthyl methyl(3-methylphenyl)thiocarbamate; N-Methyl-N-(3-methylphenyl)carbamothioic Acid O-2-Naphthalenyl Ester; Methyl(3-methylphenyl)carbamothioic Acid O-2-Naphthalenyl Ester; 2-Naphthyl N-Methyl-N-(3-tolyl)thiocarbamate; Aftate; Chinofungin; Dermoxin; Phytoderm; Pitrex; Sch 10144; Tolnaphthate; Tolsanil; Tonoftal; Tritin; Methyl-[3-methylphenyl]-carbamothioic acid O-2-naphthyl ester; Methyl-(3-methylphenyl)carbamothioic acid O-2-naphthyl ester; Tolnaftate

Database IDs

• CAS Number: 2398-96-1
• EC Number: 219-266-6
• MDL Number: MFCD00056611
• PubChem SID: 160963870; 46505456; 24900394
• PubChem CID: 5510
• ATC CODE: D01AE18
• CHEMBL: 83668
• Chemspider ID: 5309
• DrugBank ID: DB00525
• KEGG ID: D00381
• Unique Ingredient Identifier: 06KB629TKV
• Wikipedia Title: Tolnaftate
• Medline Plus: a682617

CALCULATED PROPERTIES

JChem

• H Acceptors: 1
• H Donor: 0
• LogD (pH = 5.5): 5.745038
• LogD (pH = 7.4): 5.7450395
• Log P: 5.7450395
• Molar Refractivity: 94.9204 cm^3
• Polarizability: 38.28467 Å^3
• Polar Surface Area: 12.47 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.87
• LOG S: -5.75
• Solubility (Water): 5.46e-04 g/l

PROPERTIES

Physical Property

• Solubility: 7.02e-05 mg/mL at 25 oC [MEYLAN,WM et al. (1996)]; Chloroform; DMSO
• Apperance: White Solid
• Melting Point: 110-111.5 °C (230-232.7°F); 110-112°C; 111-112°C
• Hydrophobicity(logP): 5.1

Safety Information

• Storage Condition: 2-8°C; Refrigerator
• Storage Warning: IRRITANT
• RTECS: FD8891300
• German water hazard class: 2
• TSCA Listed: false
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: Others
• Legal Status: OTC

Product Information

• Salt Data: Free Base

DETAILS

MP Biomedicals - 02156934

Crystalline

DrugBank - DB00525

• Drug Groups: approved
• Description: Tolnaftate is a synthetic over-the-counter anti-fungal agent. It may come as a cream, powder, spray, or liquid aerosol, and is used to treat jock itch, athlete's foot and ringworm. It is sold under several brand names, most notably Tinactin (Schering-Plough Corporation) and Odor Eaters (Combe Incorporated). Other brands are Absorbine, Aftate, Desenex, Genaspor, NP 27, and Ting.
• Indication: 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 powder aerosol may be used to prevent athlete's foot.
• Pharmacology: Tolnaftate is a synthetic over-the-counter anti-fungal agent.
• Toxicity: Oral rat LD50: 891 mg/kg. Inhalation rat LC50: > 900 mg/m3/1hr. Irritation: skin rabbit: 500 mg/24H mild. Eye rabbit: 100 mg severe. Investigated a mutagen and reproductive effector.
• Affected Organisms: Yeast and other fungi
• References: Barrett-Bee K, Dixon G: Ergosterol biosynthesis inhibition: a target for antifungal agents. Acta Biochim Pol. 1995;42(4):465-79. [Pubmed] ; Ryder NS, Frank I, Dupont MC: Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate. Antimicrob Agents Chemother. 1986 May;29(5):858-60. [Pubmed]
• External Links: Wikipedia; Drugs.com

Sigma Aldrich - T6638

Application
Tolnaftate is used to study the mechanism of ergosterol (sterol) biosynthesis at the rate-limiting step of squalene epoxidase inhibition. Tolnaftate is clinically used to treat cutaneous infections such as athlete′s foot, jock itch, and ringworm1. It also has been used as a comparator compound for antifungal efficiency studies2.
Biochem/physiol Actions
Tolnaftate prevents ergosterol biosynthesis by inhibiting squalene epoxidase. It has also been reported to distort the hyphae and to stunt mycelial growth in susceptible organisms1. Tolnaftate inhibits biosynthesis of aflatoxin.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. T6638.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - T535400

Antifungal.

REFERENCES

• Barrett-Bee K, Dixon G: Ergosterol biosynthesis inhibition: a target for antifungal agents. Acta Biochim Pol. 1995;42(4):465-79. Pubmed
• Ryder NS, Frank I, Dupont MC: Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate. Antimicrob Agents Chemother. 1986 May;29(5):858-60. Pubmed
• Fliri, A., et al.: J. Med. Chem., 52, 8038 (2009)
• Gohil, V., et al.: Nat. Biotechnol., 28, 249 (2009)
• Dresen, S., et al.: Anal. Bioanal. Chem., 396, 2425 (2009)