Tetramisole

Levamisole. The racemic mixture of the d and / isomers of tetramisole [6649-23-6] was first described in 1966. It is used as an anthelmintic against a wide variety of nematodes, including lungworms, of mminants, swine, horses, dogs, and poultry. Anthelmintic activity resides in the /-isomer, levamisole [14769-73-4], the form used. 

Chemical Name L-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]thiazole hydrochloride Common Name L-Tetramisole hydrochloride Structural Formula ... 

Groger has also reported a preliminary study on enantioselective acetyl migration in the Steglich rearrangement using one of Fu s commercially available catalysts and Birman s tetramisole-based organocatalyst [108]. 

Finally, while trying to evalnate the inflnence of the pyridine ring on the selectivity, Birman disclosed yet another family of catalysts for the acylative KR of ec-benzylic alcohols. Derived from commercially available tetramisole, benzotetramizole (BTM, 47) led to ontstanding selectivities on a wide range of alcohols (s = 100-350, Scheme 16) [155, 156]. 

Levamisole (see Chapter 26, Section Ill.e and Chapter 28, Section III) is an imidazothiazole derivative and the L isomer of D,L-tetramisole. It has activity against Ascaris and Trichostrongylus but is mainly used for its immunomodulating effects in Rheumatoid Arthritis and as adjunct therapy in some anti-cancer regimens. 

The racemic DL-tetramisole and its levo-isomer, levamisole, constitute the best-known members within this group of drugs (Fig. 4.2). Since the anthelminthic activity of tetramisole, which was first marketed in 1966, resides almost entirely in its levo-isomer, levamisole rather than the parent tetramisole is the drug currently used in most countries. 

Table VII lists biological activities that have been found for some aromatic azapentalenes. Among these, imidazo[2,l-6]thiazoles have probably been most studied, and this has partly followed the discovery454 that a tetrahydro derivative 480 possessed marked anthelmintic activity. This compound is marketed as Tetramisole (or as the L-isomer, Levamisole) and is at present one of the most effective agents for the treatment of roundworm infestations. Anthelmintic activity has been found for aromatic imidazo[2,l-6]thiazoles (Table VII), and it has been suggested331 that a 6-aryl substituent is necessary for activity in this series.

Corresponding reduced rings (cf 38, 40) can be obtained from a-aziridinyl heterocycles (37, 39). Related ring systems are obtained by formation of an alternative C—N bond, e.g. the alcohol (41) on heating with sulfuric acid affords racemic tetramisole (42) (68JOC1350). 

Infestations with parasitic worms and flukes are widespread both in humans and in animals, and their treatment requires drugs that act in a different manner from antibacterial and antiprotozoal agents. It is desirable for worms to be expelled from the body intact since the presence of dead worms in the tissues can provoke severe reactions. Such reactions are seen when filarial worms which circulate in the blood and lymph are killed by diethylcar-bamazine (264). Intestinal worms may be expelled when they are paralyzed by neuromuscular blockers such as piperazine citrate or pyrantel (265), or their metabolism may be disrupted by the anthelmintic drugs tetramisole and thiabendazole (266) which inhibit fumarate reductase, or mebendazole (267) which prevents glucose uptake by the worms. The anthelmintic activity of tetramisole is due to its laevo isomer levamisole (186). The dextro isomer has antidepressant activity. 

In 1966 the second modern broad spectrum anthelmintic, tetramisole (9), was introduced by Jannsen. The discovery of this drug followed the observation that the thiazothienol (10) was metabolized to an active compound in chickens. This was shown to be the thiazothielite (11) which led ultimately to the discovery of tetramisole (9). Later investigations showed that most of the activity of tetramisole (9) was due to the L-isomer, levamisole, which was more potent and less toxic than the D-isomer. Since their introduction, tetramisole (9) and levamisole have probably become the most widely used anthelmintics against a broad range of nematodes in pigs, sheep and poultry. Furthermore, unlike most benzimidazole carbamates, which are rather insoluble and must be given as an oral drench, levamisole may be given by the more convenient injectable route at a dose of 7.5 mg kg-1. 

Tetralins — see also Naphthalenes, tetrahydro-thermochemistry, 2, 368 Tetralones Schmidt reaction azepine synthesis by, 7, 531 Tetramisole—see Imidazo[2,I-6]thiazoie, ( )-2,3,5,6-tetrahydro-6-phenyl-... 

Common Name L-Tetramisole hydrochloride Structural Formula ... 

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