A STRUCTURE-ACTIVITY STUDY OF 4 DOPAMINE-D-1 AND DOPAMINE-D-2 RECEPTOR ANTAGONISTS, REPRESENTING THE PHENYLINDAN, PHENYINDENE, AND PHENYINDOLE STRUCTURAL CLASSES OF COMPOUNDS

Representatives of the phenylindan, -indene, and -indole classes of co mpounds (3-6) have been tested for affinity for the dopamine D-1 and D -2 receptors. The compounds all display high affinities for these rece ptors. Conformational analysis using MM2(87) and subsequent molecular least-squares superimpositions have been performed in order to determi ne if the affinities of the compounds can be rationalized by a recentl y proposed dopamine D-2 receptor-interaction model. In spite of the di fferent geometric and conformational properties, the compounds can be well accommodated into the model in their calculated lowest energy con formations. The molecular superimpositions allow the absolute configur ations of the active enantiomers of 4 and 5 to be predicted. The prese nt structure-activity study extends the receptor-interaction model by suggesting that the receptor is not very sensitive to the orientation of the p-fluorophenyl ring in 1 and 3-6 or to the exact spatial locati on of the associated fluoro substituent.