Description
Sertaconazole has been developed and launched for the
treatment of dermatological fungal infections by Ferrer
Internacional S. A. Mylan received FDA approval for
sertaconazole nitrate cream for the treatment of athlete's foot
(tinea pedis) at the end of 2003.
Uses
An imidazole antifungal agent, inhibits the synthesis of ergosterol, an essential cell wall component of fungi.
Definition
ChEBI: 1-{2-[(7-chloro-1-benzothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole is a member of the class of imidazoles that carries a 2-[(7-chloro-1-benzothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl group at position 1. It is a dichlorobenzene, an ether, a member of imidazoles and a member of 1-benzothiophenes.
Indications
Topical treatment of mycoses of the skin induced or sustained by fungi such as yeasts and dermatophytes. New formulations for the treatment of vaginal mycoses are in development.
Antimicrobial activity
Sertaconazole is a rather new broad-spectrum imidazole antimycotic with activity against almost all species of pathogenic fungi. It also has excellent activity against pathogenic yeasts.
Synthesis
2,4-Dichloro acetophenone
169 was brominated at low temperature to give bromide
intermediate 170, which was used without isolation. To the
same pot, five-fold excess of imidazole was added to give
imidazolylacetophenone 171 in 71% yield from 169.
Sodium borohydride was employed to reduce ketone 171 to
alcohol 172 in 78% yield. Racemic alcohol 172 was resolved with (-)-DIP-chloride to give its corresponding
chiral R-alcohol 173 in 80% yield. Compound 173 was then
alkylated with 3-bromomethyl-7-chlorobenzo[b]thiophene
(174) in dry DMF in the presence of potassium t-butoxide to
give the alkylation product in 68% yield. Finally, 60%
nitric acid was used to make sertaconazole mononitrate
(XXI) in 89% yield.
Solubility in organics
Fairly soluble in ethanol (1.7 %), chloroform (1.5 %); slightly soluble in acetone (0.95 %); very slightly soluble in noctanol (0.069 %). Practically insoluble in water (< 0.01 %).
