1390672-63-5Relevant articles and documents
Allyl m -trifluoromethyldiazirine mephobarbital: An unusually potent enantioselective and photoreactive barbiturate general anesthetic
Savechenkov, Pavel Y.,Zhang, Xi,Chiara, David C.,Stewart, Deirdre S.,Ge, Rile,Zhou, Xiaojuan,Raines, Douglas E.,Cohen, Jonathan B.,Forman, Stuart A.,Miller, Keith W.,Bruzik, Karol S.
, p. 6554 - 6565 (2012/09/21)
We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the 3H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC50 approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human α1β2/3γ2L GABAA receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both α1 and β3 subunits of human α1β3 GABA A receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.
