Drugs benzimidazole

Blood counts and liver function studies should be monitored during long-term therapy. The drug should not be given to patients with known hypersensitivity to other benzimidazole drugs or to those with cirrhosis. The safety of albendazole in pregnancy and in children younger than 2 years of age has not been established. 

Thiophanate is a synthetic antinematodal pro-benzimidazole drug intended for oral administration in form of a feed additive, drench, or bolus to cattle, sheep, swine, and goats. Recommended dosages are either 6-7 mg/kg bw/day for at least 14 days in the feed or 50-60 mg/kg bw as a single oral dose. Thiophanate is considered a nontoxic benzimidazole. 

Microtubules The microtubules of the cytoskeleton and mitotic spindle consist of tubulin polymers. These tubulins are heterogeneous among species. Structural features of alpha-tubulins in helminths may account for the selective toxicity of benzimidazole drugs (eg, mebendazole). These agents bind to microtubules in helminths to block transport processes. 

Another recent copper-mediated approach for the construction of benzimidazole drugs uses a somewhat different strategy than those previously described. Inspired in part by Driver and Shen s iron(II)-catalyzed synthesis of benzimidazoles from aryl azides,Lee and co-workers have described a copper-catalyzed three-component synthesis of benzimidazoles from an o-haloaniline, an aldehyde, and sodium azide. Under the optimized conditions, the reaction proceeds with CuCl (5 mol%), TMEDA (5 mol%) in DMSO at 120 to afford benzimidazoles in moderate to high yields. The mechanism for this reaction has not been fully explored, but may involve the intermediacy of a 2-iminoaryl azide. This approach has been applied toward the one-pot synthesis of tiabendazole, a fungicide, and parasiticide sold under the trade names Mintezol and Tesederm. 

Vitamin Bi (thiamine), B2 (riboflavin). Be (pyridoxine), B12 (cyanocobalamine), C (ascorbic acid), E (tocopherols), folic acid, pantothenic acid, K, K2, K3 (menadione), PP factor (nicotinamide), biotin Benzimidazole drugs, bromoisovalerylurea, cardiazol, chlorhexidine, dicoumarol, dulcin, isoniazid, 2-nitrofuran derivatives, parabens (4-hydroxybenzoic acid esters), phenacetin, phenylbutazone (and its metabolite oxyphenbutazone), propipocaine, quercetin, rutin, thiomersal (sodium ethylmercurithiosalicylate)... 

Some antiparasitic drugs, notably the macrocyclic lactones, have already been addressed in Chapter 6. This chapter will examine the toxic effects of other compounds that are widely used, or have been used, as antiparasitic drugs in animals. In Europe and elsewhere, the main anthelmintic drugs are the benzimidazoles and levamisole. The major benzimidazole drugs are thiabendazole, albendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxiben-dazole, triclabendazole and albendazole sulphoxide (ricobendazole, albendazole oxide). Febantel and netobimin are two prodrugs that in vivo are converted to fenbendazole and albendazole, respectively. Levamisole is the levo ( ) isomer of (dextro isomers. Tetramisole has been superseded by levamisole. These and some other antiparasitic drugs are discussed in this chapter. 

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. 

Oxatomide (l- 3- [4-(diphenylmethyl)-l-piperazinyl] propyl)-l,3-dihydro-2H-benzimidazol-2-one) is an antiallergy drug. Akamatsu has reported that oxatomide decreases neutrophil-generated superoxide anion and hydrogen peroxide formation in a dose-dependent manner. The authors hypothesize that the drug is inhibiting NADPH-dependent oxygen metabolism within the neutrophil (Akamatsu et al., 1993). 

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... 

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... 

A large number of patent applications has been filed, most recently describing imidazothiazoles [70], oxazolopyridines [71], benzimidazoles [72], benzothiazoles [73] and imidazopyridines [74] as sirtuin modulators, however it is not yet possible to determine which compound classes will prove most promising. Overall, due to their potential applications as new drug candidates for various indications, the class III HDAC inhibitors are currently a rapidly growing field of interest. 

Antiemetic drugs, 27 (1990) 297 Antifilarial benzimidazoles, 25 (1988) 233 Antifolates as anticancer agents, 25 (1988)... 

S. Sharma, Design of New Drugs for Helminth Diseases Lead Optimization in Benzimidazoles , in Advances in Drug Research , Eds. B. Testa, U. A. Meyer, Academic Press, London, 1994, Vol. 25, p. 103- 172. 

Esomeprazole is the S-isomer of omeprazole (Prilosec), which is a mixture of the S- and R-isomers. Prilosec, for many years a best selling drug, is 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-IH-benzimidazole. Its empirical formula is (Ci7Hi8N303S)2Mg-3H20 with a molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. 

It should be noted that there are normally three names associated with a drug the trade or proprietary name (e.g., Nexium), generic or nonproprietary name (esomeprazole), and a specific chemical name for the active ingredient. In the case of esomeprazole, the active ingredient is the S-isomer of benzimidazole. 

Omeprazole is an antiulcer drug. It is a proton pump inhibitor. This substituted benzimidazole inhibits gastric acid secretion to help acid/peptic disorders and duodenal ulcers. It interferes with the proton pump in the mucous lining of the stomach, the last stage of acid production. It can turn off stomach acid in as little as one hour. Lansoprazole (no. 12) has a similar structure. 

---