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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/08 10:32:00」(JST)

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Tolnaftate is a synthetic thiocarbamate used as an anti-fungal agent that may be sold without medical prescription in most jurisdictions. It is supplied as a cream, powder, spray, and liquid aerosol. Tolnaftate is used to treat fungal conditions such as jock itch, athlete's foot and ringworm. It is sold under several brand names, including Absorbine, Aftate, Genaspor, Lamisil AF, Mycil (Reckitt Benckiser), NP 27, Odor Eaters (Combe Incorporated), Scholl, Tinactin (Bayer), Tinaderm, and Ting.

Synthesis

Tolnaftatesynthesis: U.S. Patent 3,334,126 GB 697897 FR 1337797 ^[1]

Equimolar amounts of 2-naphthol and thiophosgene are combined to make a monosubstituted product of thiophosgene.

The synthesis of tolnaftate is a three-step process first involving 2-napthol with a base, to deprotonate the acidic phenol hydrogen. NaH, NaNH₂ are commonly used. Other common bases may also be used with the same effect. Treatment of N-methyl-m-toluidine with CS₂ and CH₃Br results in a thiocarbamate intermediate that reacts with the negatively charged oxygen on the deprotonated 2-napthol, displacing the -SCH₃ group and forming the final product.

Mechanism

Although the exact mechanism of action is not entirely known, it is believed to inhibit squalene epoxidase,^[2] an important enzyme in the biosynthetic pathway of ergosterol (a key component of the fungal membrane) in a similar way to allylamines.^[3]

Uses

Tolnaftate has been found to be generally slightly less effective than azoles when used to treat tinea pedis (athlete's foot). It is, however, useful when dealing with ringworm, especially when passed from pets to humans.^[4]

References

^ Noguchi, T.; Hashimoto, Y.; Miyazaki, K.; Kaji, A.; J. Pharm. Soc. Japan 1968, 88, 335
^ Ryder NS, Frank I, Dupont MC (May 1986). "Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate". Antimicrob. Agents Chemother. 29 (5): 858–60. doi:10.1128/aac.29.5.858. PMC 284167. PMID 3524433.
^ "antifung". Retrieved 2008-07-09.
^ Crawford F, Hart R, Bell-Syer S, Torgerson D, Young P, Russell I. Topical treatments for fungal infections of the skin and nails of the foot (Cochrane Review). In: The Cochrane Library, Issue 1, 2003. Oxford: Update Software.

External links

Medline's entry for tolnaftate

UpToDate Contents

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English Journal

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Studying the penetration of fatty acids into human skin by ex vivo TOF-SIMS imaging.

Kezutyte T1, Desbenoit N, Brunelle A, Briedis V.
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PMID 23713459

Japanese Journal

抗真菌薬はアトピー性皮膚炎患者Ｔ細胞のＩＬ‐４，ＩＬ‐５産生を抑制する

神田奈緒子
日本医真菌学会雑誌 45(3), 137-142, 2004
アトピー性皮膚炎患者の治療に抗真菌薬が有効であることが報告されている.アトピー性皮膚炎患者および健常者の末梢血T細胞の抗CD3,CD28抗体刺激によるTh1,Th2サイトカイン産生に対する抗真菌薬の作用について検討した.抗CD3,CD28抗体で刺激したT細胞のIL-4,IL-5の放出量はアトピー性皮膚炎患者では健常者と比較して高かった.アゾール系抗真菌薬ケトコナゾール,イトラコナゾール,ミコナゾー …
NAID 130003672089

モルモット足白癬モデルにおけるTolnaftate外用剤の治療効果

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The Japanese journal of antibiotics 54(6), 323-330, 2001-06-25
NAID 10006802141

抗菌活性を有する 2-アニリノ-4-フェニルチアゾールの合成およびそのステロール生合成阻害活性

汲田泉,野田薫
日本農薬学会誌 26(2), 136-142, 2001-05-20
我々は先に, T.mentagrophytesやB.cinereraに対して高い抗菌活性を示すと同時に, それに対応した強いスクワレンエポキシダーゼ阻害活性を示す3-(2, 6-ジクロルフェニル)-5-フェニルアミノ-1, 2, 4-チアジアゾール類を見出した.スクワレンエポキシダーゼ阻害剤は二つの疎水性ドメインと, それらをつなぐスペーサーからなるというNussbaumerらのモデルを参考にして …
NAID 110001713237

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リンク元	「トルナフタート」「トルナフテート」

「トルナフタート」

Tolnaftate
Systematic (IUPAC) name
	O-2-naphthyl methyl(3-methylphenyl)thiocarbamate
Clinical data
Trade names	Tinactin
AHFS/Drugs.com	monograph
MedlinePlus	a682617
Legal status	OTC;
Identifiers
CAS Registry Number	2398-96-1
ATC code	D01AE18
PubChem	CID: 5510
DrugBank	DB00525
ChemSpider	5309
UNII	06KB629TKV
KEGG	D00381
ChEBI	CHEBI:9620
ChEMBL	CHEMBL83668
Chemical data
Formula	C19H17NOS
Molecular mass	307.41 g/mol
	SMILES S=C(Oc2ccc1c(cccc1)c2)N(c3cc(ccc3)C)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 ; Key:FUSNMLFNXJSCDI-UHFFFAOYSA-N ;
Physical data
Melting point	110 to 111.5 °C (230.0 to 232.7 °F)
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