Antiemetic drugs benzamides

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],... 

Sulpiride is a member of a series of neuroleptics, the benzamides, of which the antiemetic drug metoclopramide is another example. The benzamides have a lower propensity to cause extrapyramidal side effects, probably because they show a high degree of selectivity for the D2 dopamine receptors. 

Further substitution of benzoic acid leads to a drug with antiemetic activity. Alkylation of the sodium salt of p-hydroxy-benzaldehyde (8) with 2-dimethylaminoethyl chloride affords the so-called basic ether (9). Reductive amination of the aldehyde in the presence of ammonia gives diamine, 10. Acylation of that product with 3,4,5-trimethoxybenzoyl chloride affords trimetho-benzamide (11). ... 

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