256456-73-2Relevant academic research and scientific papers
Enantiospecific enzyme-catalysed resolution of novel N,N-disubstituted α-amino acid phenolic ester derivatives using pig liver esterase
Bennett, D.Jonathan,Buchanan, Kirsteen I.,Cooke, Andrew,Epemolu, Ola,Hamilton, Niall M.,Hutchinson, Edward J.,Mitchell, Ann
, p. 362 - 365 (2001)
R-Amino acid esters 1, 2 and 3 are novel compounds possessing hypnotic activity. On attempting an asymmetric synthesis of these molecules, racemisation was observed when reacting bis(2-methoxyethyl)amine with α-bromo intermediate 4. In vitro plasma stability studies showed that the R enantiomers had much greater resistance to esterase-mediated degradation than the corresponding S enantiomers. This observation led to the use of commercially available pig liver esterase to prepare 1, 2 and 3 on a multigram scale. The crystal structures of 1 and 2 are reported and confirm R configuration.
α-amino acid phenolic ester derivatives: Novel water-soluble general anesthetic agents which allosterically modulate gabaa receptors
Anderson,Belelli,Bennett,Buchanan,Casula,Cooke,Feilden,Gemmell,Hamilton,Hutchinson,Lambert,Maidment,McGuire,McPhail,Miller,Muntoni,Peters,Sansbury,Stevenson,Sundaramt
, p. 3582 - 3591 (2007/10/03)
In the search for a novel water-soluble general anesthetic agent the activity of an α-amino acid phenolic ester lead, identified from patent literature, was markedly improved. In addition to improving in vivo activity in mice, good in vitro activity at GABAA receptors was also conferred. Within the series of compounds good enantioselectivity for both in vitro and in vivo activity was found, supporting a protein-mediated mechanism of action for anesthesia involving allosteric modulation of GABAA receptors. α-Amino acid phenolic ester 19, as the hydrobromide salt Org 25435, was selected for clinical evaluation since it retained the best overall anesthetic profile coupled with improved stability and water solubility. In the clinic it proved to be an effective intravenous anesthetic in man with rapid onset of and recovery from anesthesia at doses of 3 and 4 mg/kg.
