Resistance benzimidazoles

Tetraaniinobiphenyl (3,3 -diaminobenzidine), produced from o-chloro nitrobenzene, is used in the manufacture of high-temperature resistant benzimidazole polymers (PBI), which are produced by reaction with diphenyl isophthalate (Hoechst-Celanese),... 

Polybenzaylene benzimidazoles (pyrrones) Polybenzoxazoles Thermally stable to 600°C (1112°F) insoluble in common solvents good mechanical properties. Stable in air to 500°C (932°F) insoluble in common solvents except sulfuric acid nonflammable chemical resistant film. 

Although it was proposed that inhibition of HCMV DNA maturation by the benzimidazole ribonucleoside BDCRB is mediated through the UL89 gene product, and resistance to TCRB maps to the two ORFs UL89 and UL56, there was no cross-resistance of an HCMV AD 169 sulphonamide-resistant strain to BDCRB (Reefschlaeger et al. 1999). 

Other chemicals evaluated but not yet adopted commercially include organophosphorus compounds, triphenyltin compounds, quaternary ammonium salts, imidazoles, benzimidazoles, carbamates and the precocene anti-juvenile hormones [517]. Although none of the above has found use as an insect-resist agent, several have been used as antimicrobial agents for textiles. 

Some interesting organic chemistry is involved in the synthesis of chlorite-resistant brighteners for acrylic fibres. None of these compounds is easy to make and methods for preparation of the starting materials can be complex. Much manufacturing know-how is involved. One route for introduction of the benzimidazole nucleus into structure 11.55 is shown in Scheme 11.22. Preparation of the chemically rather simpler benzoxazole grouping in product 11.56 is shown in Scheme 11.23. 

There is a need for development of new anthelmintics, as resistance in livestock has been recorded against benzimidazoles, imidothiazoles and the avermectin/macrocyclic lactones, in addition to older drugs... 

Poly(benzimidazole)s possess excellent thermal stability, flame resistance, and outstanding chemical resistance. The solubility of hexafluoroisopropyli-dene-unit-containing poly(benzimidazole)s is remarkably improved.24 They are readily soluble in strong acids such as formic acid, concentrated sulfuric acid, and methanesulfonic acid and in aprotic polar solvents such as DMAc and NMP. The polymer from tetramine (23) is soluble even in m-cresol and pyridine. 

Spotts, R. A., F. L. Lukezic, and N. L. Lacasse. The effect of benzimidazole, cholesterol, and a steroid inhibitor on leaf sterols and ozone resistance of bean. Phytopathology 65 45-49, 1975. 

Imidazole was converted by hydrogenation over platinum oxide in acetic anhydride to 1,3-diacetylimidazolidine in 80% yield, and benzimidazole similarly to 1,3-diacetylbenzimidazoline in 86% yield [480. While benzimidazole is very resistant to hydrogenation over platinum at 100° and over nickel at 200° and under high pressure, 2-alkyl- or 2-aryl-substituted imidazoles are reduced in the benzene ring rather easily. 2-Methylbenzimidazole was hydrogenated over platinum oxide in acetic acid at 80-90° to 2-methyl-... 

Benzimidazoles are highly selective. Oomycete fungi are insensitive to the benzimidazoles, as are higher plants. The reason for the distinct differences in sensitivity is unknown but probably depends on single structural differences of the microtubule binding site. Resistance of this type, if stable, spreads rapidly and results in catastrophic disease control... 

Phenylcarbamates, for example, diethofencarb (Figure 4.15) are active against fungi that are resistant to benzimidazoles. The two groups may... 

Their development and commercial success was favoured by the coincidence of resistance to benzimidazole fungicides. 

L.G. Davidse and W. Flach, Differential Binding of Benzimidazol-2-yl Carbamate to Fungal Tubulin as a Mechanism of Resistance to this Antimitotic Agent in Mutant Strains of Aspergillus nidulans J. Cell. Biol., 1977, 72, 174-193. 

The air dried poly(arylene ether benzimidazole) films displayed excellent resistance to methylene chloride, hydraulic fluid (Skydrol) and jet fuel (HyJet IV)... 

Heat stabilizers can be selected from benzothiazoles, benzimidazoles hydrazine compounds, and cation exchange materials (73). Moreover, the addition of heat stabilizers results in an improvement of the impact resistance. 

Several related analogues of the benzimidazoles are also anthelmintics including the imidazopyridine (5), tioxidazole (6), and the prodrugs, thiophanate (7) and febantel (8). However, although the benzimidazoles and related anthelmintics have proved a rich source of drugs, there is now evidence of widespread resistance to them, particularly in sheep parasites. Moreover, some benzimidazole carbamates are suspect in respect of teratogenicity and mutagenicity. 

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,... 

Another group of drugs that bind to microtubules are benzimidazole and related compounds. These have been used widely to treat infection by parasitic nematodes in both humans and animals. Unfortunately resistance has developed rapidly. 

Incubation of free-living stages of the parasite in drug can be very useful, the classical example being the egg hatch test for benzimidazole resistance in nematodes (see Coles et a ., 1992). As eggs of Fasciola are killed by... 

Pape, M., Posedi, J., Failing, K., Schnieder, T. and von Samson-Himmelstjerna, G. (2003) Analysis of the beta-tubulin codon 200 genotype distribution in a benzimidazole-susceptible and -resistant cythostome population. Parasitology 127, 53-59. 

The ability to oxidize to a corresponding hydroxyl-containing heterocycle is typical for dihydro derivatives of pyrazolo[l,5-a]pyrimidines 331 and pyri-mido[l,2- ]benzimidazoles 333. Simply dissolving these compounds in CHC13, DMF and alcohols at ambient conditions produces compounds 334 and 336 as major products together with heterocycles 340 and 342 (in some cases the latter products were not observed) [168, 293]. It is interesting to note that compounds 334-336 have a very high resistance to the action of... 

Prichard [15] has shown that thiabendazole inhibits the NADH oxidation in the presence of fumarate in Haemonchus contortus homogenates, which are sensitive to benzimidazole derivatives. Later studies, however, in benzimidazole-resistant H. contortus [16, 17] provide contrary evidence. 

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