title: Liquid chromatographic studies on the aqueous solution conformation of substituted benzamides related to remoxipride.
abstract: 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.
authors.affiliation: Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Alabama 36849.
authors.forename: C R
authors.initials: CR
authors.lastname: Clark
authors.forename: F T
authors.initials: FT
authors.lastname: Smith
authors.forename: M R
authors.initials: MR
authors.lastname: Clark
authors.forename: L E
authors.initials: LE
authors.lastname: Garcia-Roura
mesh_terms: D014150:Antipsychotic Agents / Q000032:analysis* / Q000737:chemistry; D001549:Benzamides / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D006860:Hydrogen Bonding; D017330:Remoxipride
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D017330:Remoxipride