Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents

Abstract

Considering the importance of hydantoin derivatives in treatment of status epilepticus, four 5-phenylhydantoins, whose lipophilicities were estimated to be similar to that of phenytoin, were synthesized. Evaluation of their anticonvulsant activities was performed on rats by subcutaneous pentylenetetrazol seizure test and intravenous pentylenetetrazol threshold test, and spontaneous locomotor activity test was used to assess possible sedative effects. X-ray analysis of three compounds suggested that certain analogies might be drawn between interactions in crystal packing and biological interactions responsible for their anticonvulsant activity. It was found that 5-ethyl-5-phenyl-3-propylhydantoin exhibits the most favorable pharmacological properties among the synthesized compounds, i.e., anticonvulsant activity comparable to phenytoin with lower liability for induction of sedation in rats.

Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles

“…48,49 The racemic products used as HPLC standards were synthesized via Bucherer-Bergs reaction of the corresponding ketones for comparison. 50,51 The results are summarized in Table 1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 …”

Synthesis, structure and biological properties of active spirohydantoin derivatives

“…Analozi sorbinila (25) koji pokazuju aktivnost ka inhibiciji aldoza reduktaze enzima (ALR2) (šema 10), proizvod su reakcije 2,3-dihidrotiopirano-(2,3-b)-piridin-4(4H)-ona (24), kao i njegovog metil analoga, sa kalijum-cijanidom i amonijum-karbonatom u vodeno--alkoholnoj sredini [5].…”

Supramolecular structure of 5-methyl-5-phenyl hydantoin and hydrogen-bonding patterns in 5,5′-substituted hydantoins

“…Just the anticonvulsant properties of phenytoin are responsible for the synthesis of many hydantoin analogs [13]. Nowadays, phenytoin has found new applications due to the neuro-and cardioprotective properties [14]. In addition, a number of other biological activities of hydantoin derivatives as herbicides and fungicides are known [15,16].…”

“…This multicomponent reaction begins from an aldehyde or a ketone and their ready availability makes this reaction an attractive method for the synthesis of hydantoins [14,22].…”