5-HT6 receptor antagonists: lead optimisation and biological evaluation ofN-aryl and N-heteroaryl 4-amino-benzene sulfonamides

RO-04-6790 (6a) has been identified in a random screen for 5-HT6 receptor a ntagonists. In a medicinal chemistry optimisation program a series of analo gs comprising N-heteroaryl- and N-arylbenzenesulfonamides have been synthes ised and investigated for their binding affinity. Compounds with a log D pr ofile indicative of brain penetration have been subjected to in vivo testin g for reversal of a scopolamine-induced retention deficit in a passive avoi dance paradigm. (C) 2001 Editions scientifiques et medicales Elsevier SAS.