α-Amino(4-aminophenyl)thiomethylene-2-(trifluoromethyl)benzeneacetonitrile; Configurational equilibria in solution

• Published in: Bioorganic chemistry Vol. 113; p. 104955
• Main Authors: McElhinny, Charles J, Lewin, Anita H, Brieaddy, Larry, Fix, Scott, Imler, Gregory H, Deschamps, Jeffrey, Mascarella, S Wayne, Seltzman, Herbert H, Anantha Reddy, P, Carroll, F Ivy
• Format: Journal Article
• Language: English
• Published: 01-08-2021
• ISSN: 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2021.104955

Inconsistent results have been reported for the effects of the mitogen-activating extracellular kinase (MEK) inhibitor α-[amino(4-aminophenyl)thio]methylene-2-(trifluoromethyl)benzeneacetonitrile (SL 327) on ethanol-induced conditioned place preference (EtOH-CPP). Since such inconsistencies may be due to the configurational composition of administered SL 327, the interconvertibility of the geometric isomers of this class of compounds has been investigated. This study provides conditions for determination of configurational composition of this class of compounds by HPLC and by 1H NMR and reports details of configurational equilibria as a function of medium and time in solution along with solubility data for SL 327 in aqueous DMSO. The results suggest that the apparently inconsistent results reported for CPP-EtOH may be due to the administration of suspension vs. solutions, as well as to different configurational compositions of SL 327.Inconsistent results have been reported for the effects of the mitogen-activating extracellular kinase (MEK) inhibitor α-[amino(4-aminophenyl)thio]methylene-2-(trifluoromethyl)benzeneacetonitrile (SL 327) on ethanol-induced conditioned place preference (EtOH-CPP). Since such inconsistencies may be due to the configurational composition of administered SL 327, the interconvertibility of the geometric isomers of this class of compounds has been investigated. This study provides conditions for determination of configurational composition of this class of compounds by HPLC and by 1H NMR and reports details of configurational equilibria as a function of medium and time in solution along with solubility data for SL 327 in aqueous DMSO. The results suggest that the apparently inconsistent results reported for CPP-EtOH may be due to the administration of suspension vs. solutions, as well as to different configurational compositions of SL 327.