Piperazine was initially utilized as a solvent for uric acid before its introduction as an anthelmintic agent in 1953. When entering the bloodstream, the drug undergoes partial oxidation while the rest is eliminated without alteration. Piperazine exhibits a remarkable ability to dissolve uric acid and generate a soluble urate outside the body. However, its clinical effectiveness has not been consistently demonstrated. Introduced as an anthelmintic in 1953, piperazine compounds exert their anthelmintic effects by inducing paralysis in parasites, enabling the host organism to effectively eliminate or expel the intruding organisms.

A significant number of modern drugs incorporate a piperazine ring within their molecular composition. These compounds can mainly be categorized into phenylpiperazines, benzylpiperazines, diphenylmethylpiperazines (benzhydrylpiperazines), pyridinylpiperazines, pyrimidinylpiperazines, or tricyclics (where the piperazine ring is linked to the heterocyclic portion through a side chain).

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Example Reaction of Piperidines:

Piperazine can undergo acylation reactions, where the amine groups react with acyl halides or acid anhydrides to form amides. This reaction is commonly used to introduce functional groups onto the piperazine ring.

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References:

[1]Laras Y, Garino C, Dessolin J, et al. New N 4-substituted piperazine naphthamide derivatives as BACE-1 inhibitors[J]. Journal of enzyme inhibition and medicinal chemistry, 2009, 24(1): 181-187.

[2]Alghamdi S, Alshehri M M, Asif M. The Neuropharmacological Potential of Piperazine Derivatives: A Mini-Review[J]. Mini-Reviews in Organic Chemistry, 2022, 19(7): 798-810.