52839-87-9Relevant articles and documents
Synthesis and structure-activity relationship studies for hydantoins and analogues as voltage-gated sodium channel ligands
Zha, Congxiang,Brown, George B.,Brouillette, Wayne J.
, p. 6519 - 6528 (2007/10/03)
We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing an effective non-hydantoin ligand. To further understand structural features that result in optimum binding, here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [3H]-batrachotoxinin A 20-α-benzoate ([3H]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore, which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.
Stereoselective anticonvulsant activity of the enantiomers of (±)-2-hydroxy-2-phenylbutyramide
Meza-Toledo,Ortega-Gonzalez,Juarez-Carvajal,Carvajal-Sandoval
, p. 756 - 759 (2007/10/02)
The enantiomers of the anticonvulsant DL-2-hydroxy-2-phenylbutyramide (1) were prepared by resolving the (-)-quinine and (+)-1-phenylethylamine salts of the acids. The optically active acids were then esterified and reacted with ammonia to give (+)-1 and (-)-1. Optical purity of the amides was greater than 99.9% enantiomeric excess by chiral HPLC. Examination of the infrared spectra of the enantiomers and the racemate of 1 in chloroform solution showed identical spectra, but the spectrum of the racemate in a KBr disc was somewhat different from those of the pure enantiomers. Pharmacologically, 1 and its enantiomers have a similar significant anticonvulsant activity at peak drug effect against pentylenetetrazol seizures, but a variation in the time between the enantiomers was found with the anticonvulsant activity. In the rotarod ataxia test (-)-1-possessed the lowest neurotoxicity.
SYNTHESIS OF α-HYDROXIAMIDES VIA THE CYANOSILYLATION OF AROMATIC KETONES
Grunewald, Gary L.,Brouillette, Wayne J.,Finney, Jay A.
, p. 1219 - 1220 (2007/10/02)
The trimethylsilyl ethers of the cyanohydrins of aryl-alkyl ketones and diaryl ketones afforded the corresponding α-hydroxyamides upon hydrolysis with HCl or HNO3/HCO2H.The method is advantageous for ketones do not readily undergo addition of HCN.
