20445-34-5Relevant academic research and scientific papers
Solvent-free synthesis of quaternary α-hydroxy α-trifluoromethyl diazenes: The key step of a nucleophilic formylation strategy
Matador, Esteban,Monge, David,Fernández, Rosario,Lassaletta, José M.
, p. 4042 - 4050 (2016/07/21)
An efficient, scalable and operationally simple one-pot, 2-step strategy for the nucleophilic formylation of trifluoromethyl ketones is presented. The key step is an unprecedented diaza-carbonyl-ene reaction of formaldehyde tert-butyl hydrazone and triflu
Comparative molecular field analysis and synthetic validation of a hydroxyamide-propofol binding and functional block of neuronal voltage-dependent sodium channels
Brown, Milton L.,Eidam, Hilary A.,Paige, Mikell,Jones, Paulianda J.,Patel, Manoj K.
scheme or table, p. 7056 - 7063 (2009/12/24)
Voltage gated sodium channels represent an important therapeutic target for a number of neurological disorders including epilepsy. Unfortunately, medicinal chemistry strategies for discovering new classes of antagonist for trans-membrane ion channels have
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
The substrate specificity of the heat-stable stereospecific amidase from Klebsiella oxytoca
Shaw, Nicholas M.,Naughton, Andrew B.
, p. 747 - 752 (2007/10/03)
The substrate specificity of the heat-stable stereospecific amidase from Klebsiella oxytoca was investigated. In addition to the original substrate, 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, the amidase accepted 2-hydroxy-2-(trifluoromethyl)-butanamide and 3,3,3-trifluoro-2-amino-2- methylpropanamide as substrates. Compounds with larger side chains and compounds where the hydroxyl group was substituted with a methoxy group, or in which the CF3 group was substituted by CCl3, were not accepted. The biotransformation is a new synthetic route to (R)-(+)-3,3,3- trifluoro-2-amino-2-methylpropanoic acid, and its related (S)-(-)-amide, and to (R)-(+)-2-hydroxy-2-(trifluoromethyl)-butanoic acid and its related (S)-(-)-amide.
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).
α-TRIFLUOROMETHYL-α-HYDROXY CARBOXYLIC ACIDS
Soloshonok, V. A.,Gerus, I. I.,Yagupol'skii, Yu. L.,Kukhar', V. P.
, p. 1298 - 1303 (2007/10/02)
The methyl esters of α-trifluoromethyl-α-hydroxy carboxylic acids were obtained by the reaction of methyl trifluoropyruvate with organometallic reagents (Cd, Mg, Zn).The characteristic features of the reactions in relation to the nature of the alkylating agent were demonstrated.
