Mapping the dopamine receptor. 2. Features derived from modifications in the rings A/B region of the neuroleptic butaclamol

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Abstract
Several analogs of the neuroleptic agent butaclamol having modifications in the rings A/B region of the molecule were synthesized. Pharmacological evaluation identified the benzo[5,6]cyclohepta analog isobutaclamol as equipotent to butaclamol. The molecular structure of the compound was analyzed and the results were used for mapping the central dopamine receptor. A planar catechol primary binding site composed of .alpha. and .beta. regions was identified and its minimal dimensions deduced. Its locus with respect to the N location site and its complementary H bond donor site was specified. Using a Cartesian coordinate system a receptor model is proposed which incorporates the above-mentioned features. The receptor model was used to rationalize the chirality of the central dopamine receptor.