5-Ht6 Receptor Antagonists. V. Structure – Activity Relationship of (4-Phenylsulfonyloxazol-5-yl)amines

Both novel and previously reported (4-phenylsulfonyloxazol-5-yl)amine derivatives containing a substituted sulfonyl group were studied in order to discover highly active 5-HT6 receptor antagonists. A new pharmacophore model of 5-HT6 receptor antagonists was proposed based on the structure—5-HT6 antagonist activity relationship. It was established that the activity of the synthesized compounds depended strongly on the nature of the amine located vicinal to the sulfonyl. The most active ligands were methyl-(4-phenylsulfonyloxazol-5-yl)amines. Replacing the methyl by a bulkier alkyl radical and conversion to tertiary amines was accompanied by a dramatic reduction of their activity for 5-HT6 receptors.