Resistance benzamides

In contrast to the aforementioned monosubstitutions, much less is known about the effect of disubstitution. It appears that such benzamides are resistant to hydrolysis. The metabolic fate of nitromide (3,5-dinitrobenzamide, 4.63), a chicken-feed additive for the prevention of coccidosis, was investigated in rats. The metabolite 3-amino-5-nitrobenzoic acid (4.64), formed by ni-tro reduction and hydrolysis, was excreted in only trace amounts. Nitromide was metabolized mainly via nitro reduction [36], Similarly, no hydrolysis was... 

Other examples of secondary benzamides include the therapeutic class of orthopramides, which are, again, markedly resistant to hydrolysis. Thus, hydrolysis of the amide bond is a minor metabolic pathway in humans for the antiemetic drug metoclopramide (4.76) [49]. Clebopride (4.77), an anti-dopaminergic agent, was found to be hydrolyzed to a limited extent in rabbit liver homogenates and in dogs to 4-amino-5-chloro-2-methoxybenzoic acid (4.78) and to the amine 4.79 [48] [50], Attempts to detect in vivo formation of this metabolite in rats, rabbits, or humans were not successful [50],... 

The salicylimides (4.169) were found to be markedly more resistant to chemical hydrolysis than 4.166. These compounds were hydrolyzed exclusively at the distal amide bond, meaning that hydrolysis produced only sali-cylamide (4.170) and not salicylic acid. This behavior has been ascribed to steric hindrance by the 2-OH group. An intramolecular general base catalysis does not seem to be involved since, as stated, the salicylamides were less reactive than the corresponding benzamides. The rate of plasma-catalyzed hydrolysis of the A-acylsalicylamides was also dependent on the nature of... 

In contrast to the case where aniline is used as the nucleophile, the benzamide reaction can be improved by utilizing dioxygen in the reaction mixture since 11 is resistent to autoxidation. Under aerobic conditions the nitrobenzene radical anion is readily trapped by O2 generating superoxide and nitrobenzene (Figure 10) (11). This reaction pathway inhibits the formation of azoxybenzene by diverting the electron transfer cascade and ultimately utilizing dioxygen as the terminal oxidant. Thus, under aerobic reaction conditions 12 is the only observed reaction product. 

Representative compounds believed to bind at the benzamide site on the basis of evidence from competitive binding or cross-resistance studies (discussed below) are shown in Fig. 16.1.3. Although these compounds differ from zoxamide in their relative toxicity toward different organisms, they appear to bind to the same domain on y -tubulin. Selective toxicity may be governed by structural differences between organisms in this domain. 

Since its first commercial use in 2001, there have been no reports of reduced pathogen sensitivity to zoxamide. Laboratory studies to investigate the potential for resistance development to the benzamide class have been carried out with zoxamide [24], and zarilamide [25], a benzamide that binds to the same site as zoxamide on jS-tubulin [7]. In these studies, attempts to isolate resistant mutants in different Oomycetes using chemical mutagenesis, UV irradiation or adaptation were unsuccessful. These results suggest that the risk for resistance development to zoxamide in its commercial target pathogens is relatively low. 

Horsman MR. Nicodnamide and other benzamide analogues as agents for overcoming hypoxic cell radiation resistance in tumours (a review). Acta Oncologica 1995 34 571-587. 

The sensitivity of the chemical amplification resist is improved by PEB. However, the resolution power of the resist is decreased by PEB because of the diffusion of acids in the film during baking. The diffusion length of acid is reported to be 25 nm during 95°C PEB for 100 s after exposure. - Addition of an organic base such as triphenylamine and benzamide improved resolution of the CA resist to less than 0.1 pm. ... 

We have studied the influence of the two inhibitors of the enz3mie poly(ADP-ribose) polymerase, benzamide (BZA) and nicotinamide (NA) on N-methyl-N -nitro-N-nitroso-guanidine (MNNG), X-ray, and UV-induced killing and 8-azaguanine (AZ) resistant mutation in V79 Chinese hamster cells. 

Fig. 3. gives kinetics of recovery for density inhibited cells exposed to H2O2. Here, 4 hr of delay before trypsinization was sufficient to show the maximum recovery. The presence of benzamide clearly inhibited this recovery process. Fig. 4. shows the yield of mutants due to UV irradiation of density inhibited cells. The phenotypic end point selected for the study was resistance to 8-azaguanine. Immediately after UV exposure, cells were diluted for mutation expression or given a delay time before mutation... 

Fig. 4. (right) UV induced mutant frequency (resistance to 8-azaguanine) in density inhibited V-79 cells. The symbol ( ) represents the yield without any delay in trypsinization (A) represents 24 hr delay in trypsinization ( ) represents 24 hr delay in presence of SmM benzamide. 

Sensitivities to X, y and UVC-radiations have been related to impaired DNA repair processes LY-S cells have been foimd to repair DNA dsb (double strand breaks) more slowly than the more radiation-resistant LY-R cells (3) LY-R cells are nucleotide excision-deficient, in contrast with the more UVC-resistant LY-S cells (4,5). In this work we review experimental data (5, 6-8) concerning LY cell response to combined UVC + Bz (benzamide) and Bz in combination with X or y rays. These results are best explained by assuming an impaired DNA ligase function in LY-S cells. 

We have shown earlier that the toxicity of endotoxin can be prevented to a large extent by antagonists of ADP-ribose metabohsm (1). On the other hand there are some indications that muramyldipeptide (MDP) interferes with the this metabolism also (2). It was reported in 1980 that MDP, in combination with trehalose dimycolate, could induce resistance against influenza viras infection (3). In this chapter we are dealing with the influence of muramyldipeptide and benzamide upon the mouse hepatitis virus type 3 (MHV3). 

The thermo-oxidative cross-linking of nylon 6 and the resistance to oxidation of its graft copolymers with polyacrylonitrile have been studied. The thermal and thermal oxidative degradation of poly(/w-phenylene isophthalamide) and other aromatic polyamide compositions, together with comparative studies on the mechanisms of degradation of poly(p-benzamide) and poIy(p-phenylene terephalamide) have all been reported. 

Stabiiizers borate base supplemented with azole or thujaplicin guar gum benzamide is water resistant biocide Clausen, C A Yang, V, Int. Biodeter. Biodeg., 59, 20-24, 2007Das, D Ara, T Dutta, S Mukherjee, A, Bioresource Technol., 102, 5878-83, 2011. 

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