Antimycotics derivative

Because of their limited, activity, small spectmm, and side effects, the older topical antimycotics have generally been surpassed by newer antimycotic chemotherapeutic agents. These newer antimycotics for topical use iaclude the imida2ole derivatives clotrimazole, miconazole, econazole, isoconazole, sulconazole, fenticonazole, oxiconazole, bifonazole, butoconazole, ziaoconazole, tioconazole, and the triazole derivative, terconazole (Table 2) (5—7). The iatroduction of the azole derivatives represents a milestone ia the treatment of mycoses. 

Clotrimazole. The imidazole derivative clotrimazole (6) was iatroducedia 1969. Clotrimazole [23593-75-1] or l-((9-chloro-a,a-diphenylbenzyl)imidazole is a water-iasoluble antimycotic for topical appHcation, with a broad-spectmm activity against mycoses of the skin and the vagiaa. 

Other imidazole derivatives include clotrimazole (Fig. 5.20B), miconazole (Fig. 5.20C) and econazole (Fig. 5.20D), all of which possess a broad antimycotic spectrum... 

Bonazzi et al. [18] reported the determination of miconazole and other imidazole antimycotics in creams by supercritical fluid extraction and derivative ultraviolet spectroscopic method. Cream based pharmaceuticals were mixed with celite and anhydrous sodium sulfate and extracted by supercritical fluid extractor (SFE) with... 

Kublin and Kaniewska [52] used a gas chromatographic method for the determination of miconazole and other imidazole antimycotic substances. The conditions have been established for the quantitative determination of miconazole and the other drugs, which are present in pharmaceuticals such as ointments and creams. The column, packed with UCW-98 on Chromosorb WAW, and flame-ionization detector were used. The statistical data indicate satisfactory precision of the method, both in the determination of imidazole derivatives in substances and in preparation. 

Triazolylcyclopropane derivatives are endowed with antimycotic properties [125]. They are also prepared as plant growth regulators and fungicides for instance 93 (R = unsubstituted and substituted aryl, heteroaryl) markedly inhibited the growth of rice, cotton and soybeans in hot tests [126]. l-(l,2,4-Triazolyl)-2-(2,4-dichlorophenyl)cyclopropane 94, is a more effective fungicide against Podosphaera leucotricha and a better growth retardant in rice and soybeans than the (l,2,4-triazolyl)pentenone 95, Eq. (36) [127]. 

Clotrimazole, is an imidazole derivative and has a broad antimycotic spectrum of action in vivo, which includes dermatophytes, yeasts, moulds etc. 

The utility of some of these products for side-chain modification has also been demonstrated. For example, 4-chloro-3-formylpyridine undergoes the Hantzsch reaction to give a 4-(3-chloropyridine)-l,4-dihydropyridine derivative (88%). (4-Chloro-3-pyridyl)diphenylmethanol affords aza-analogues (65-70%) of the antimycotic agent chlortrimazol by reaction with thionyl chloride and imidazole derivatives (88JHC81). 

The antimycotic activity of a number of substituted 3-(3,3,3-trichloro-2-hydroxyprop-l-yl)benzofurans has been reported. Diuretic and other activities have been observed in a number of substituted aminobenzofuran-2-carboxylic acid derivatives. a- 2-Benzofuranyl) acrylic acid has exhibited a marked depressive ataratic and hypotensive activity (61MI31200), while 5-cinnamoylbenzofurans, e.g. (499), have been examined for hypertensive, vasodilating and spasmolytic activities (70GEP1933178). 

Salicylic acid [69-72-7] - [SALICYLIC ACID AND RELATED COMPOUNDS] pol 21) - [COSMETICS] pol 7) - pENTAL MATERIALS] pol 7) -acetic acid from acetylation of [ACETIC ACID AND DERIVATIVES - ACETIC ACID] pol 1) -acetylation of [ACETIC ACID AND DERIVATIVES - ANHYDRIDE] pol 1) -m antiacne products [COSMETICS] Pol 7) -as antidandruff agent [COSMETICS] Pol 7) -as dye primary pYES AND DYE INTERMEDIATES] pol 8) -as rubber chemical pUBBER CHEMICALS] pol 21) -synthesis of [MICROBIALTRANSFORMATIONS] pol 16) -use as disinfectants piSINFECTANTS AND ANTISEPTICS] pol 8) -m Whitfield s ointment [ANTIPARASITIC AGENTS - ANTIMYCOTICS] pol3)... 

In similar studies, the reduction potentials of 1,2-benzothiazole derivatives in DMF were correlated to antimycotic activity [166], and those of 1,3,5,7-substituted-1,3-dihydro-2H-l, 4-benzodiazepin-2-ones and benzodiazepine-2-thiones in dimethylformamide (DMF)-water solutions were correlated to inhibition of orientation reactions and to protection from electric shock [167]. 

Phenylthiosemicarbazones cyclize easily to triazolo derivatives when heated alone or refluxed in high-boiling solvents. Phenylthiosemicarbazones 95 were refluxed in DMF and cyclized into 4,5-dihydro[l,2,4]tria-zolo[3,4-t/][l, 5]benzothiazepine-l(2tf)-thiones (96), which can exist either in the thioamidic or in the iminothiolic form. Infrared spectra showed that the thioamidic form seems to be preferred. By PTC alkylation of 96 with methyl iodide, ethyl chloroformate, or chloroacetic acid, the corresponding -substituted derivatives 97 were obtained (Scheme 28) (91MI1). Many of the compounds were cytotoxic and hence not screened further others were tested as antibacterial, antimycotic, and antiviral agents, but no appreciable activity was observed. 

Apart from the triazole derivatives, a small group of imidazoles is active against plant pathogens (Figure 5). The most important compounds in this group are imazalil and prochloraz. However, most of the Important antimycotic EBI s originate from the imidazole series. Two of these antimycotics are bifonazole and clotrimazole, which resemble fluotrimazole. These two antimycotics will be dis-... 

In a recent East German review some biological activities of triazoles (1,2,4- and 1,2,3-) have been described (8iMl4lloo). The virostatic, cytostatic, antimicrobial and antimycotic activities of derivatives of 1,2,3-triazolecarbonamides are discussed. Furthermore, 4- or 5-halomethyl-1,2,3-triazoles, c.g. (420a), can be used as radiomimetica and show cancero-... 

Niphimycin, an antimycotic antibiotic derived from Actinomyces hygroscopicus, is effective against both der-matomycosis and onychomycosis, with a 16-26% success rate in the latter. Tolerance is reportedly good, but there is a notable lack of recent data (SEDA-12, 236). 

Other imidazole derivatives include clotrimazole (Fig. 10.22B), miconazole (Fig. 10.22C) and econazole (Fig. 10.22D), all of which possess a broad antimycotic spectrum with some antibacterial activity and are used topically. Miconazole is used topically but can also be administered by intravenous or intrathecal injection in the treatment of severe systemic or meningeal fungal infections. Newer imidazoles are (a) ketoconazole (Fig. 10.22E),... 

Bonazzi D, Cavrini V, Gatti R, Boselli E, Caboni M. Determination of imidazole antimycotics in creams by supercritical-fluid extraction and derivative UV spectroscopy. J Pharm Biomed Anal 1998 18 235-240. 

Various derivatives are also active as anthelmintics,61-63 muscle relax-ants,2,64 diuretics,65 antimycotics,66 antihypertensives,67 and anticholesterics.68 The metabolism of 4-[3-dimethylaminopropyl]-3,4-dihydro-2-(l-hydroxyethyl)-3-phenyl-2f/-1,4-benzothiazine in vivo by rats, dogs, and monkeys has been studied, and at least five metabolites were isolated.69... 

Developmental Topical Antimycotics. Most of the topical antimycotics still being developed are azole derivatives (mostly imidazole), including butoconazole, oxiconazole, omoconazole, zinoconazole, and sulconazole (Fig. 3). Generally speaking, these newer azoles offer no additional therapeutic advantages compared to existing substances. These drugs are already available in certain countries, but are not yet commercialized on a worldwide scale. 

Starting from the hypothesis that azo compounds with an ability to form active carbonium ions in vivo are biologically active, Biichel et al. (1972,1975) synthesised several derivatives of 1-trityl azoles. They established in extensive research work that the derivatives particularly active are those which contain only one substituent in one of the phenol rings, and in which the azole ring remains unsubstituted. This led to the very active antimycotic clotrimazole (see Section 5.7.1), which nowadays plays an important role in the local therapy of human mycoses, and to fluo-trimazole, of specific activity against powdery mildews. 

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