Synthesis and structure-activity relationship of the isoindolinyl benzisoxazolpiperidines as potent, selective, and orally active human dopamine D4 receptor antagonists.

A new class of potent dopamine D(4) antagonists was discovered with selectivity over dopamine D(2) and the alpha-1 adrenoceptor. The lead compound was discovered by screening our compound collection. The structure-activity relationships of substituted isoindoline rings and the chirality about the hydroxymethyl side chain were explored.