Triazole resistance

Potential for Resistance. Resistance appears to be the major potential obstacle to optimal use of many of the new fungicides. It is clear from the experiences with triazole resistance in powdery mildew... 

A unique feature of prothioconazole is that it shows equally good activity against both cereal eyespot species, OcuUmacula yallundae (= Tapesia yallundae = Pseudocercosporella herpotrichoides W-type) and O. acuformis = Tapesia acuformis = Pseudocercosporella herpotrichoides R-type) whereas all other triazoles used against eyespot control only O. yallundae effectively. Surprisingly, in cross resistance studies prothioconazole revealed a unique profile as far as no positive cross resistance to either triazole-resistant or to prochloraz-resistant isolates could be detected [94]. 

This is not discussed in detail since mechanisms of resistance have been carefully reviewed (Ghannoum and Rice 1999). It was pointed out that resistance has not been associated with modification of the structure. For the 1,2,4-triazoles that have been widely used, their effect is due to inhibition of the synthesis of ergosterol that is the dominant component of fungal cell membranes. Resistance is generally associated with modification of the target enzymes, for example, the epoxidation of squalene (Terbinafine) or 14a-demethylase (Fluconazole). Resistance of Candida albicans to the azole antifungal agent fluconazole demonstrated, however, the simultaneous occurrence of several types of mechanism for resistance (Perea et al. 2001) ... 

Synthesis was directed towards metabolic stability and this was found in the bis-triazole series of compounds. Metabolic stability is achieved by the relative resistance of the triazole moiety to oxidative attack, the presence of halogen functions on the phenyl grouping, another site of possible oxidative attack, and steric hindrance of the hydroxy function, a site for possible conjugation. 

The 3-alkylthio groups in 1,2,4-thiadiazoles are difficult to replace. Thus, 3-alkylthio-l,2,4-thia-diazoles resist the action of aniline at 100°C, ammonia at 120°C, molten urea and ammonium acetate however, hydrazine attacks 3-methylthio-l,2,4-thiadiazole (142) forming 3-amino-1,2,4-triazole (143) (Equation (21)) <65AHC(5)119>. In contrast to 3-alkylthiogroups, 5-sulfonyl groups in... 

Information concerning the chemistry of meso-ionic 3-alkyl- and 3-aryl-l,2,3,4-oxatriazol-5-ones (271) is limited, but further investigation may well be encouraged by reports of pronounced hypotensive activity. 3-Cyclohexyl-1,2,3,4-oxatriazol-5-one (271, R = cyclohexyl) is resistant to attack by dilute mineral acid, but warm concentrated sulfuric acid gives cyclohexanol and carbon dioxide. In contrast, acid hydrolysis of 3-phenyl-l,2,3,4-oxatriazol-5-one (271, R = Ph) yields phenyl azide. Meso-ionic 3-cyclohexyl-l,2,3,4-oxatriazol-5-one shows two unusual reactions its photoirradiation in benzene gives cyclohexanone and heating with diphenylacetylene )delds l-cyclohexyl-4,5-diphenyl-1,2,3-triazole (276) rather than the expected 2-cyclohexyl-4,5-diphenyl-1,2,3-triazole. 

H-1,2,3- and 1//-1,2,4-Triazoles are resistant to base-induced ringopening, but 2-phenyl-l,2,3-triazole-4-carboxylic acid (49) has been decarboxylated and cleaved by heating with barium hydroxide (69AJC1915). 

The almost exclusive use of triazoles for cereal powdery mildew control up to the mid-1980s has resulted in a shift in Erysiphe populations toward reduced sensitivity or resistance to this class of fungicides. However, use has continued because field performance of most triazoles has remained adequate (43). Decreased azole sensitivity in the Septoria population to azoles has also been noted. 

Well over 100 plant pathogens have become resistant to various fungicides under field conditions. Failure of the acyl alanines, benzimidazoles, thiophanates, carboxanilides, dicarboximides, hydroxypyrimidines, some organophosphates, and most of the antibiotics has occurred. In other cases, a moderate decrease in sensitivity without a rapid loss of disease control has been observed as in the case of sterol biosynthesis inhibitors (triazoles, pyrimidines, and imidazoles) and organophosphates. The most effective approach is to use fungicides having different modes of action in combination,... 

Bis(l,2,3-triazol-2-yl)stilbene brighteners have high efficiencies and good lightfastness and are very resistant to chemical bleaches. They are employed as brighteners for cotton and polyamides. An example is 4,4 -bis(4-phenyl-l,2,3-triazol-2-yl)stilbcnc-2,2 -disulfonic acid dipotassium salt (32) [52237-03-3] [59],... 

Selected with amitrole/atrazine combinations with cross-resistance to all triazines, triazinones, ureas, and triazoles. Selected with diuron, and cross-resistance to all triazines as well. 

The introduction of a second aza group into the 5-membered rings reduces further the susceptibility to electrophilic attack. Triazoles,212, 213 oxadiazoles214, 215 and thiadiazoles216-218 are practically completely resistant to electrophilic substitution unless powerful electron-releasing substituents are present. No quantitative studies on the reactivities of these rings have been made. 

Resistance has not thus far been a serious problem for the EBI s. Although numerous resistant mutants have been developed in laboratory studies, resistance problems in the field have not occurred. However, recent investigations related to the use of a triazole fungicide on barley indicate that resistant strains of pathogenic fungi may be increasing (26). The fact that there have not been major problems may be associated with the nature of the mode of action and the fact that mutants appear to have reduced fitness (11, 18). In other words, the genetic alterations conducive to survival in the presence of these compounds may also reduce fitness. 

An attempt to formulate a poly(4-hydroxy styrene)-based resist was less than completely successful because the difference in the rates of dissolution were too small to be used to give high contrast images. Other small molecules were added to the NDS/novolac resist and these were also found to have a profound effect upon the performance of the resist, particularly the development properties. When it was necessary to obtain higher dissolution rates, several triazoles and sulfonamides were found to improve the rate of development in the exposed areas without causing unacceptable thickness losses in the unexposed areas. Dyes incorporated to minimize problems of reflection and scattered light were also found to alter the dissolution behavior of the resist coating. 

These are naphthalene dlcizoquinones as photoactive compounds, benzo-triazoles as development enhancement agents, and dyes to reduce exposure from reflected light. The latter compounds have been added to resist formulations which already contain a photoactive compound in addition to the polymer binder. 

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