Hydantoins

Hydantoins are a class of heterocyclic compounds based on the hydantoin ring, a five‑membered ring containing two carbonyl groups at positions 2 and 4 in an imide framework. The parent compound, hydantoin (2,4-imidazolidinedione), can be variably substituted at nitrogen atoms or at carbon positions to give a wide family of derivatives. Substituted hydantoins are widely used in medicinal chemistry, particularly for anticonvulsant activity.

Synthesis and derivatives commonly involve cyclization reactions that form the hydantoin ring from urea or carbamoyl derivatives, sometimes via glyoxal or glyoxylate condensations. The resulting compounds can bear a range of N-alkyl, N-aryl, or aryl‑methyl substituents. A well-known subgroup includes 5,5-disubstituted hydantoins, such as 5,5-diphenylhydantoin, which corresponds to the marketed anticonvulsant phenytoin and related drugs like ethotoin and mephenytoin.

Pharmacology and use are dominated by anticonvulsant activity. Hydantoins act primarily by modulating neuronal excitability through stabilization of the inactivated state of voltage-gated sodium channels, reducing repetitive firing. This mechanism underlies their effectiveness in partial and generalized tonic–clonic seizures. Some hydantoins may have additional actions on calcium channels or neurotransmitter systems, but sodium channel modulation is central for most clinical derivatives.

Clinical considerations include a narrow therapeutic index and potential drug interactions due to hepatic enzyme induction. Adverse effects can range from neurological symptoms to gingival hyperplasia and hirsutism with long-term use. Hydantoins remain a historic and, in some settings, still-used scaffold in anticonvulsant therapy and medicinal chemistry research.