Luliconazole Antifungal [4547

Country of origin Originator First introduction Introduced by Trade name CAS registry no Molecular weight

Japan

Nihon Nohyaku Japan

Nihon Nohyaku/Pola Lulicon 187164-19-8 354.28

Luliconazole is a member of the imidazole class of antifungal agents, with specific utility as a dermatological antimycotic drug. It was launched last year in Japan as a topical agent for the treatment of athlete's foot. Luliconazole is an optically active drug with (R)-configuration at its chiral center. It is structurally related to la-noconazole, which has been marketed as a racemic mixture since 1994. As with other azole antifungal drugs, the mechanism of action of luliconazole is the inhibition of sterol 14-a-demethylase, and subsequently, inhibition of ergosterol biosynthesis. In C. albicans, luliconazole inhibits ergosterol biosynthesis with an IC50 of 14 nM, and it is about 2.5-fold more potent than lanoconazole (IC50 = 36 nM), and 28-fold more potent than bifonazole (IC50 = 3 90 nM). The corresponding (S)-enantiomer of luliconazole is virtually inactive. In vitro, luliconazole exhibits strong antifungal activity against Trichophyton mentagrophytes and Trichophyton rubrum, with mean minimum inhibitory concentration (MIC) values of 0.0093 and 0.0015 mg/mL, respectively. In general, it has high activity against filamentous fungi except zygomycetes, and good-to-moderate activity against yeast-like fungi. It also has activity against C. albicans, which is slightly lower than fluconazole, as well as activity against Aspergillus fumigatus, which is at least 60-fold lower than itraconazole. The in vivo activity of luliconazole against dermatophytes has been evaluated in the guinea pig model of tinea pedis. In this study, a 1% topical solution of luliconazole, administered once daily for seven days, achieved complete mycologic cure. Additionally, there were no occurrences of relapse for up to 16 weeks after the treatment. No data is currently available on the clinical efficacy of luliconazole. The chemical synthesis of luliconazole involves the condensation of 1-(cyanomethyl)imidazole with carbon disulfide to produce a dithioate intermediate, and subsequent alkylation with either the mesylate derivative of (S)-1-(2,4-dichlorophenyl)-2-bromoethanol or the bis-mesylate derivative of (S)-1-(2,4-dichlorophenyl)ethane-1,2-diol.

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