In certain embodiments, the present disclosure is directed to methods and uses for treating a mammal having an epileptic seizure disorder or being at risk for having an epileptic seizure disorder, comprising administering certain herein disclosed isolated fenfluramine enantiomers that are surprisingly effective as anti-epilepsy drugs (AEDs), despite having lower anti-seizure potency than fenfluramine racemate, by virtue of also being less cardiotoxic than fenfluramine racemate. Preferred embodiments contemplate treatment of Dravet syndrome; other preferred embodiments contemplate treatment of other epileptic seizure disorders.
-
Paragraph 0201; 0203
(2020/02/15)
Process for the production of the isomers (R) and (S)-Alpha-methyl-3-(trifluoromethyl)benzeneethanamine
Process for the production of the isomers (R) and (S)-α-methyl-3-(trifluoromethyl)benzeneethanamine, the second being usable as intermediate in the synthesis of the anorexic drug dexfenfluramine (INN), which comprises carrying out a stereospecific reductive amination of 1-(3-trifluoromethyl)phenyl-2-propanone with (R) or (S)-α-methylbenzylamine under hydrogen atmosphere in the presence of a catalyst and in debenzylating the resulting diastereoisomer (R),(R) or (S),(S)-N-(1-phenylethyl)-α-methyl-3-(trifluoromethyl)benzeneethanamine by treatment with hydrogen and catalyst.
-
(2008/06/13)
Process for the production of the isomers (R) and (S)-α-methyl-3(trifluoromethyl)benzeneethanamine
Process for the production of the isomers (R) and (S)-α-methyl-3-(trifluoromethyl)benzeneethanamine, the second being useful as intermediate in the synthesis of the anorexic drug dexfenfluramine (INN), which comprises carrying out a stereospecific reductive amination of 1-(3-trifluoromethyl)phenyl-2-propanone with (R) or (S)-α-methylbenzylamine under a hydrogen atmosphere in the presence of a catalyst and debenzylating the resulting diastereoisomer (R),(R) or (S),(S)-N-(1-phenylethyl)-α-methyl-3-(trifluoromethyl)benzeneethanamine by treatment with hydrogen and a catalyst.
-
(2008/06/13)
Homochiral (R)- and (S)-1-heteroaryl- and 1-aryl-2-propanols via microbial redox
Preparation of various heteroaryl propanols 2a-g and of the corresponding propanones 3a-g as starting materials for microbial redox is described. The kinetic resolution of the racemic propanols 2a-g is obtained via oxidation with Pseudomonas paucimobilis and Bacillus stearothermophilus [(R)-alcohols, ee 74-100%]. Similar results are achieved with 3-(2- hydroxypropyl)trifluoromethylbenzene 7 (44%, ee 100% of the (R)-alcohol 6). The reduction of the propanones 3a-d and 3g with baker's yeast and other fungi gives the (S)-alcohols (ee 100%). The pure (S)-alcohols are also obtained by reduction of 1-[3-(trifluoromethyl)phenyl]-2-propanone 7. 1- [(4,4-Dimethyl)-2-(Δ2)oxazolinyl]-2-propanone 3e and 1[2-(Δ2)- thiazolinyl)-2-propanone 3f are not reduced. The heterocyclic rings of (S)- 5-(2-hydroxypropyl)-3-methylisoxazole 2d and of (S)-2-(2-hydroxypropyl)-4- methylthiazole 2g are deblocked to the homochiral enamino ketone 8 (78%) and to the protected β-hydroxy aldehyde 9 (73%), respectively. The (R)-3-(2- hydroxypropyl)trifluoromethylbenzene 6 is transformed into the homochiral precursor of (S)-fenfluramine 10 (overall yield 65%).