Obtaining the Phenytoin and the Influence of Different Reaction Parameters (original) (raw)
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Synthesis and evaluation of phenytoin derivatives as anticonvulsant agents
2,5-Dioxo-4,4-diphenylimidazolidine-1-carboxylic acid (2) was reacted with methyl ester of different amino acids (1a-c) and substituted benzhydrols (3a-b) in pyridine and in the presence of N,N dicyclohexyl carbodiimide (DCC) to yield a series of the title compounds, methyl 2-(2,5-dioxo-4,4-diphenylimidazolidine-1-carboxamido) substituted propanoate (4a-c) and benzhydryl 2,5-dioxo-4,4-diphenyl imidazolidine-1-carboxylate (5a-b).
Synthesis and anticonvulsant activity of new phenytoin derivatives
European Journal of Medicinal Chemistry, 2013
Dioxo-4,4-diphenylimidazolidine-1-carboxylic acid (2) was reacted with methyl ester of different amino acids (1a-c) and substituted benzhydrols (3a-b) in pyridine and in the presence of N,N dicyclohexyl carbodiimide (DCC) to yield a series of the title compounds, methyl 2-(2,5-dioxo-4,4-diphenylimidazolidine-1-carboxamido) substituted propanoate (4a-c) and benzhydryl 2,5-dioxo-4,4-diphenyl imidazolidine-1-carboxylate (5a-b). The structures of these compounds were established on the basis of their spectral (IR, 1 H-NMR) data. These newly synthesized derivatives of phenytoin were evaluated in terms of anticonvulsant activity.
One-Pot Synthesis of Phenytoin Analogs
Russian Journal of Organic Chemistry, 2004
A series of phenytoin analogs (5,5-diphenylimidazolidine-2,4-dione or 5,5-diphenyl-hydantoin) were synthesized in 65–75% yield from the corresponding substituted benzils. The same products were also obtained directly from α-hydroxy ketones via one-pot procedure.
A high yield synthesis of phenytoin and related compounds using microwave activation
African Journal of Pure and Applied Chemistry, 2011
A reaction system is described to synthesize phenytoin, a major antiepileptic drug, and structurally related compounds using a two-step approach. The first step involves the treatment of a benzil derivative by thiourea in dimethylsulfoxide (DMSO) in aqueous KOH under microwave activation. The resulting 2-thiohydantoin was then oxidized to the corresponding hydantoin using perhydrol in dimethylformamide (DMF) in acetic acid. Both steps proceeded in high yield. For example, with this method, phenytoin was obtained in 80% yield while by the conventional Biltz's method, the yield rarely exceeded 50%. The first step can be advantageously performed using microwave activation. Our process is based on a mechanistic approach supported by theoretical PM3 calculations.
Pakistan journal of pharmaceutical sciences, 2018
The narrow therapeutic index, non-linear pharmacokinetics and unpredictable absorption require regular therapeutic monitoring of phenytoin. The influence of genetic differences, sex, age and race on the phenytoin plasma levels and its metabolites is well recognized. This study is aimed at evaluating phenytoin plasma drug concentration and its relationship with clinical response, persistent seizures and toxicity in different gender and various age groups of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of phenytoin in various sub-groups of epileptic patients for enhancing the safety, efficacy and minimizing the toxicity of phenytoin. A total of 48 plasma samples of epileptic patients for measuring the plasma phenytoin concentration were received. Only patients displaying persistent seizures or suspected of adverse effects were requested for drug monitoring. All these samples were analyzed for therapeutic drug monitoring with Enzyme-...
Journal of Organic Chemistry, 2014
The eco-friendly preparation of 5-and 5,5disubstituted hydantoins from various amino ester hydrochlorides and potassium cyanate in a planetary ball-mill is described. The one-pot/two-step protocol consisted in the formation of ureido ester intermediates, followed by a base-catalyzed cyclization to hydantoins. This easy-handling mechanochemical methodology was applied to a large variety of αand β-amino esters, in smooth conditions, leading to hydantoins in good yields and with no need of purification steps. As an example, the methodology was applied to the "green" synthesis of the antiepileptic drug Phenytoin, with no use of any harmful organic solvent.
Crystal modification of phenytoin using different solvents and crystallization conditions
International journal of pharmaceutics, 2003
Phenytoin crystals having different types of habits, were prepared by recrystallization from ethanol and acetone solutions under different conditions (cooling rate or crystallization temperature, solvent evaporation and watering-out techniques). Scanning electron microscopy, X-ray powder diffractometry, FT-IR spectrometry and differential scanning calorimetry were used to investigate the physical characteristics of the crystals. The dissolution behavior and compaction properties of various batches of crystals were also studied. It was found that using watering-out technique as a crystallization method, produced thin plate crystals, while the crystals obtained by other methods were needle shape for alcoholic solutions and rhombic for acetone solutions. X-ray diffraction spectra and differential scanning calorimetry studies, did not show any polymorphic change. The dissolution rate of different crystals was lower than that of untreated samples. The compacts of phenytoin crystals produ...
Application of green solvent in synthesis of thiophenytoins using aryl thioureas
2012
Phenytoin (5,5’-dipenylimidazolidine-2,4-dione) and Thiophenytoin (5,5-diphenyl-2-thioimidazolidine-4-one) are the prime examples of anticonvulsant agent. According to reported procedure, they are synthesized by condensation of benzil and urea in presence of base (30% w/v NaOH) using ethanol as solvent which itself acts as CNS stimulant. Removal of solvent after synthesis is most difficult and non-assured process. Therefore in the present work by application of green chemistry principles thiophenytoins were synthesized by condensation of benzil and sub. aryl thioureas in presence of base and water as green solvent. These compounds were characterized on the basis of its spectral (UV,IR, 1H NMR) data.
Journal of Pharmacokinetics and Biopharmaceutics, 1982
Phenytoin plasma level and toxicity data were compared in a three-way crossover study performed in 18 patients at steady state. Formulations compared were a rapid and a slow release capsule and an oral solution. Plasma concentration-time integrals and maximum plasma phenytoin levels were significantly greater for the rapid release capsule and solution than for the slow release capsule. The incidence of nystagmus and toxicity did not differ for the three treatments, but the occurrence of mental symptoms was more frequent for the oral solution, possibly because of the solvent used in this formulation.