Liquid chromatographic studies on the aqueous solution conformation of substituted benzamides related to remoxipride.
A series of disubstituted benzamides related to the sterically hindered 2,6-dimethoxybenzamide drugs, such as remoxipride, are prepared. The structure-retention relationships for these compounds are studied on hydrocarbon stationary phases in various hydroorganic mobile phases. The 2,6-dimethoxybenzamide displays a very low capacity factor under these reversed-phase conditions, suggesting that steric crowding prevents the formation of an amide-methoxy N-H...O intramolecular hydrogen bond. The corresponding 2-hydroxy-6-methoxybenzamide shows a dramatic increase in affinity for the hydrocarbon stationary phase, which is characteristic of strong intramolecular hydrogen bonding in these compounds. These results suggest that the aromatic ring--carbonyl aqueous solution conformation is almost 90 degrees in amides like remoxipride and changes to coplanarity upon demethylation of one methoxy group.
Clark
C R
CR
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Alabama 36849.
Smith
F T
FT
Clark
M R
MR
Garcia-Roura
L E
LE
D014150:Antipsychotic Agents / Q000032:analysis* / Q000737:chemistry; D001549:Benzamides / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D006860:Hydrogen Bonding; D017330:Remoxipride
D014150:Antipsychotic Agents; D001549:Benzamides; D017330:Remoxipride