Antifungal agents

The antifungal agent clotrima2ole [23593-75-1] has been prepared by the Friedel-Crafts reaction of (9-chloroben2otrichloride [2136-89-2] and ben2ene in the presence of AlCl, followed by treatment with imida2ole (50). 

A. Keerkenaar, in R. A. Fromtiing, ed.. Recent Trends in the Discovey, Development and Evaluation of Antifungal Agents, J. R. Prouse, Science PubHshers, Barcelona, Spain, 1987, p. 523. 

Griseofulvia [126-07-8] (54) coataias the pblorogluciaol aucleus. It is an important oral antifungal agent ia humans and animals, elaborated by certain strains of Penicillium. One synthesis of griseofulvia is based oa the appropriately substituted pblorogluciaol (196). Uvaretia [58449-06-2] (55), which is extracted from JJvaria acuminata inhibits lymphocytic leukemia (200). 

Nifuroxime. The anti form of the oxime prepared from 5-nitro-2-furancarboxaldehyde and hydroxylarnine, has been marketed for topical use as an antibacterial or an antifungal agent (1,17). 

Amoxicillin — see Penicillin, D-n-amino-p-hydroxybenzyl-Amozonolysis cycloalkenes, 6, 876 Amphotericin B antifungal agent veterinary use, 1, 211... 

Nucleoside antibiotics biosynthesis, 1, 88-90 Nucleosides oxa analogues, 3, 1085 as pharmaceuticals, 1, 153 protected, 5, 316 Nucleosidin occurrence, 5, 603 Nupharolutine synthesis, 2, 393 Nybomycin applications, 6, 667 Nybomycin, deoxy-applications, 6, 667 Nystatin antifungal agent veterinary use, 1, 211... 

Fluconazole (4) (s the first member of a new generation of orally acti ve antifungal agents, highly effective in the treatment of dermal and vaginal infections [6, 7] S-Fluorocyrtosine (5) is also used to treat serious systemic fungal infections [5]... 

The Corey-Chaykovsky reaction incited some applications in medicinal chemistry. During the synthesis of analogs of fluconazole, an azole antifungal agent, treatment of 49 with 1 led to the corresponding epoxide, which was subsequently... 

For example, Ghorab and coworkers exploited the classical Biginelli reaction to synthesize a variety of potentially active antifungal agents such as 56 from DHPM 55. ... 

The antifungal agent, dianithazole (76), is prepared by cleaving the ether function of 2-dimethylamino-6-ethoxybenzothia-zole (74) with aluminum chloride in chlorobenzene and then alkylating the sodium salt of the resulting phenol (75) with 2-diethylaminoethyl chloride. 

Removal of the nitro group results in an alteration of antimicrobial spectrum leading to a series of antifungal agents. For example, reaction of 2,4-dichloroacetophenone with glycerol and tosic acid leads to dioxolane Under bromin-... 

If the displacement reaction is carried out between imidazole derivative and thiophene analogue the antifungal agent tiaconazole (40) results. A rather slight variant of... 

Two closely related pyridotriazines have been described as antifungal agents. Displacement of halogen on nitro-... 

Nafimidone (93), an anticonvulsant compound, also contains an imidazole moiety It seems to have been discovered by accident during a search for antifungal agents Its synthesis is straightforward involving displacement with imidazole of the activated chlorine atom of chloro-methyl-p-naphthylketone (92) [32]... 

Bifonazole (109) is claimed to be remarkably non-toxic and is marketed as a topical antifungal agent overseas. It can be conveniently synthesized in the by now familiar way by reduction of p-phenylbenzophenone (108) with borohydride, conversion to the chloride with thionyl chloride, and then imidazole displacement to bifonazole (109) [39]. 

Stopher and Gage used size-exclusion chromatography (SEL) coupled to reversed phase HPLC for the direct injection of plasma in the analysis of an antifungal agent, voriconazole (12). Their system consisted of three columns, i.e. first a size-exclusion... 

Figure 15.5 Separation of Voriconazole and an internal standard by using SEC-HPLC. Adapted from Journal of Chromatography, B 691, D.A. Stopher and R. Gage, Determination of a new antifungal agent, voriconazole, by multidimensional high-perfomiance liquid chromatography with direct plasma injection onto a size exclusion column , pp. 441 -448, copyright 1997, with permission from Elsevier Science.

The sensitivity of barley to the toxin increases as the stage of germination advances. This may be partially explained by the presence of antifungal agents in the young plant whose activity is reduced with age (8,12). Further progress on the chemistry of this material is reported by Stoessl (14). 

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