116271-85-3Relevant academic research and scientific papers
Exalted resonance demands in the substituent effects on the acetolyses of 2-arylethyl trifluoromethanesulfonates destabilized by cn and cf3 groups
Usui, Satoshi,Tsuboya, Shoko,Umezawa, Yukthiro,Hazama, Ken,Okamura, Mutsuo
experimental part, p. 254 - 260 (2009/05/30)
Substituent effects on the acetolysis rates of 2-aryl-l-cyano-l- (trifluoromethyl)ethyl trifluoromethanesulfonates (α-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (ss-OTf) were investigated by using LArSR equation. The obtained p and r+ values were p = -3.28, r+ = 0.98 and p = -3.48,r+ = 0.93 for the acetolysis of α-OTf and ss-OΥi, respectively. The obtained p values are comparable to those for typical aryl-assisted solvolyses, but the r+ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted solvolyses are assisted by the strong participation of the ss-aryl group.
Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants
Schenck, Hilary A.,Lenkowski, Paul W.,Choudhury-Mukherjee, Indrani,Ko, Seong-Hoon,Stables, James P.,Patel, Manoj K.,Brown, Milton L.
, p. 979 - 993 (2007/10/03)
Themisone, also known as Atrolactamide, was found, in the 1950s, to be a very potent anticonvulsant. It was hypothesized that the -CF3 substitution would maintain the anticonvulsant activity. Anticonvulsant testing of our novel compounds by the
Design, synthesis, and evaluation of analogues of 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide as orally available general anesthetics
Choudhury-Mukherjee, Indrani,Schenck, Hilary A.,Cechova, Sylvia,Pajewski, Thomas N.,Kapur, Jaideep,Ellena, Jeffrey,Cafiso, David S.,Brown, Milton L.
, p. 2494 - 2501 (2007/10/03)
We have recently discovered a novel class of compounds that have oral general anesthetic activity, potent anticonvulsant activity, and minimal hemodynamic effects. The 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide (1) demonstrated potent ability to reduce the minimum alveolar concentration (MAC) of isoflurane, with no effects on heart rate or blood pressure at therapeutic concentrations. Analogue 1 also had potent oral anticonvulsant activity against maximal electroshock (MES) and subcutaneous metrazol (scMET) models with a therapeutic index of 10 for MES activity. In this study, we further synthesized nine new racemic analogues and evaluated these compounds for effects on isoflurane MAC reduction and blood pressure. Preliminary data demonstrate potent reduction in the isoflurane MAC for two new compounds. Current mechanistic studies were unrevealing for effects on voltage-gated ion channels as a putative mechanism. Liposomal partitioning studies using 19F NMR reveal that the aromatic region partitions into the core of the lipid. This partitioning correlated with general anesthetic activity of this class of compounds. Further, compound 1 was used at a concentration of 1 mM and slightly enhanced GABAA current in hippocampal neurons at 10 μM. Altogether, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide exhibited excellent oral general anesthetic activity and appears devoid of significant side effects (i.e., alterations in blood pressure or heart rate).
