2- -benzimidazole Thiabendazole

Preparation of the prototype drug departs from the phenylenediamine strategy used in all of the previous examples. Condensation of thiazolo nitrile (53-2) with aniline catalyzed by aluminum chloride affords the amidine addition product (53-3). This is then converted to its reactive A -chloro derivative (53-4) by reaction with sodium hypochlorite. Treatment of that intermediate with a base such as potassium hydroxide leads directly to the cyclization product and thus the benzimidazole thiabendazole (53-6) [56]. The reaction can be rationalized by invoking as the first step the abstraction of chloride to leave behind a nitrene species such as (53-5) this would then readily insert in the CH bond at the ortho position. 

Application techniques can influence the efficacy of postharvest fungicides and, thus, alter the keeping quality of treated fruit. Application of sodium ortho-phenylphenate (SOPP) in a foam washer with an exposure time of only 15 to 20 sec is not as an effective method as a soak or drench treatment requiring 2-4 min (167). However, if proper pH control is not maintained, fruit may be burned with the soak or drench treatment (169, 170, 171). Applications of SOPP in wax were less phytotoxic (172). Within the last 14 years, development of the benzimidazoles, thiabendazole Q -(4 -thiazolyl) benzimidazole and. benoniyl Tmethyl 1-(butyl carbamoyl)-2-benzimidazole-carba-mat J, has led to the availability of fungicides with high... 

Benzimidazoles. Thiabendazole, and a few years later, benomyl, were introduced as postharvest fungicides 1n the late 1960s. These outstanding compounds (benzimidazole fungicides) provided excellent control of both fruit decay and Penicmium sporulation (1,2). 

Examples of synthetically produced and biologically active benzimidazoles are the fungicides methyl l-butylcarbamoyl-2-benzimidazole carbamate (benomyl) 5 and 2-(4 -thiazolyl)benzimidazole (thiabendazole) 6. The latter is used extensively as a preservative for fruit (E 233) and as an anthelmintic in veterinary medicine ... 

A variety of pesticides has been determined in food samples by EIA. In many cases Abs against the target compound were developed in-house. Mainly pAbs were still used, but mAbs were applied for the determination of atrazine, benzimidazoles, thiabendazoles and carbaryl. ... 

Changing the substitution pattern on the benzimidazole greatly alters the biologic activity. Thus, inclusion of a thia-zole ring affords thiabendazole (70), a drug used for the treatment of helminthiasis. 

Thiabendazole Benzimidazole, 2-(4-thiazolyl)- (8) IH-Benzi-midazole, 2-(4-thiazolyl)- (9) (148-79-8)... 

The extraction Module E3 is particularly suitable for the analysis of the partly acid-sensitive azoles (e.g., myclobutanil, propiconazole, tebuconazole, fluotrimazole, thiabendazole, carbendazim). By combining the cleanup step using a GPC column and separation on a small silica gel column, 27 azoles, four benzimidazoles and thiazoles and live imidazolines could be determined with this multi-residue method. 

The control of worm infestations of domestic animals (horse, sheep, cattle, pigs) and humans is an important therapeutic objective for which thiabendazole (60) serves as the prototype of numerous benzimidazole... 

Binding to P-tubulin. The anthelmintic benzimidazoles, such as thiabendazole and albendazole, are drugs that bind selectively to nematode... 

Thiabendazole, a benzimidazole derivative, is an antihelminthic drug used primarily to treat infections caused by... 

CASRN 148-79-8 molecular formula C10H7N3S FW 201.25 Photolytic. When thin films of thiabendazole on glass plates were exposed to sunlight for 128 d, benzimidazole-2-carboxamide and benzimidazole formed as photolysis products. Both compounds also formed when aqueous methanolic solutions of thiabendazole were subjected to UV light for 1 h (Zbozinek, 1984). 

Thiabendazole Thiabendazole, 2-(4 -thiazolyl)benzimidazole (38.1.9), is also made in the same manner—heterocyclization which occurs upon reacting o-phenylendiamine with l,3-thiazol-4-carboxylic acid [4-6]. 

Several benzimidazoles are in use for the treatment of helminthic infections. Three of these, mebendazole, thiabendazole and albendazole, are described in this section. They have a broad range of activity against many nematode and cestode parasites, including cutaneous larva migrans, trichinosis, disseminated strongyloidiasis, and visceral larva migrans. A fourth, triclabendazole, is considered as the drug of choice for Easciola hepatica therapy. 

Thiabendazole (Mintezol) inhibits fumarate reductase and electron transport-associated phosphorylation in helminths. Interference with ATP generation decreases glucose uptake and affects the energy available for metabolism. Benzimidazole anthelmintics as a class (e.g., thiabendazole, mebendazole, and albendazole), bind selectively to (3-tubulin of nematodes (roundworms), ces-todes (tapeworms), and trematodes (flukes). This inhibits microtubule assembly, which is important in a number of helminth cellular processes, such as mitosis, transport, and motihty. 

Thiabendazole (9.126), a benzimidazole, is used to treat strongyloidiasis and trichinosis. Within the parasite, thiabendazole inhibits an enzyme called fumarate reductase, resulting in death of the worm. This drug may be carcinogenic or mutagenic to the host. 

Thiabendazole is a benzimidazole compound. Although it is a chelating agent that forms stable complexes with a number of metals, including iron, it does not bind calcium. 

The mechanism of action of thiabendazole is probably the same as that of other benzimidazoles (see above). The drug has ovicidal effects against some parasites. 

Thiabendazole is much more toxic than other benzimidazoles and more toxic than ivermectin, so other agents are now preferred for most indications. Common adverse effects include dizziness, anorexia, nausea, and vomiting. Less common problems are epigastric pain, abdominal cramps, diarrhea, pruritus, headache, drowsiness, and neuropsychiatric symptoms. Irreversible liver failure and fatal Stevens-Johnson syndrome have been reported. 

The benzimidazole group of anthelminthics is derived from the simple benzimidazole nucleus and includes the thiabendazole analogues and the benzimidazole carbamates. Substitution of side chains and radicals on the benzimidazole nucleus gives rise to the individual members of this group (Fig. 4.1). 

Early benzimidazoles, such as thiabendazole, are quite soluble and quickly eliminated from the body. Newer benzimidazoles, such as albendazole, fenbenda-zole, febantel, and netobimin, are less-soluble compounds that exhibit much slower rates of elimination because they remain as solid precipitates within the gut for extended periods, increasing their efficacy against immature and arrested larvae and adult nematodes. 

A number of benzimidazoles exist as prodrugs their anthelminthic activity is due to the fact that they are metabolized in the animal body to the biologically active benzimidazole carbamate nucleus. Due to their relatively slower excretion rates, the newer insoluble benzimidazoles have fairly long withdrawal periods for edible tissues and milk in contrast to the less effective and more rapidly excreted thiabendazole analogues. Strict compliance with withdrawal periods is always necessary because of the potentially toxic and teratogenic effects of some of the benzimidazoles and their metabolites. 

Since all members of the benzimidazole anthelminthics except thiabendazole contain a benzimidazole carbamate moiety, attempts have been made to produce antibodies recognizing this structure (19). Most successful was an approach in which a carboxylated analogue of albendazole was used as hapten and coupling to the carrier protein was performed using (V-hydroxysuccinimide and morpholi-noethyl isocyanide in the presence of dimethylamino pyridine. 

Matrix solid-phase dispersion has also been applied for the determination of ivermectin residues in bovine liver (373) and milk (372), moxidectin in bovine tissues (374), thiabendazole and mebendazole in meat (66), and five and seven benzimidazoles in bovine liver (375) and milk (322), respectively. 

A direct mass spectrometric method for simultaneous detection of five benzimidazoles including levamisole, thiabendazole, mebendazole, fenbendazole, and febantel in sheep milk was reported (377). The method, which involves injection of crude milk extracts and selection and collision of the most abundant ionic species obtained under electron impact ionization, was highly sensitive and rapid. Another direct mass spectrometric approach for rapid and quantitative determination of phenothiazine in milk was also described (323). This method involves an extraction step using a Cig microcolumn disc, followed by thermal desorption of the analyte from the disc directly into an ion trap mass spectrometer. 

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