Novel tetrahydropyrido[3,2-c]pyrroles as 5-HT(7) antagonists

The synthesis and SAR for a novel series of tetrahydropyrido3,2-c]pyrroles is described. Optimization of the pendant aryl ring lead to high binding affinity at the 5-HT₇ receptor when small lipophilic groups were placed in the para position. Modification of the N-benzyl group and secondary amine were not well tolerated. A representative set of compounds was shown to be functional antagonists of the 5-HT₇ receptor.