potential antipsychotic agents 5 synthesis and antidopaminergic properties of substituted 56dimethoxysalicylamides and related compounds a series of 3substituted 56dimethoxysalicylamides iii 913 and 15 has been synthesized from the corresponding 256trimethoxybenzoic acids relaxation times t1 and carbon chemical shifts of the methoxy groups in iii showed that the 6methoxy group adopts a nearly perpendicular orientation and the 5methoxy group takes on a more coplanar orientation with respect to the ring plane in solution the salicylamides iii display a very high and stereoselective affinity for the 3hspiperone and 3hraclopride binding sites in vitro regioisomeric salicylamides iv also exhibit pronounced but lower than iii affinity for the 3hspiperone binding site the structural requirements were further assessed by studies of the related amino analogues 23 and 24 and hydroxy analogue 27 the 3bromo compound 11 flb 463 was studied in various in vivo models and compared with the dopamined2 antagonists sulpiride raclopride eticlopride and haloperidol the high potency of 11 to selectively block dopamined2 receptors in vitro and in vivo combined with indications on a low potential for motor side effects makes it a very interesting new member of the class of substituted salicylamides