Synthesis and biological evaluation of novel N ₁-phenylsulphonyl indole derivatives as potent and selective 5-HT₆R ligands for the treatment of cognitive disorders

摘要

Abstract A series of 1-[3-(4-methyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole and 1-[3-(4-ethyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole derivatives were designed and synthesized as 5-HT₆ receptor (5-HT₆R) ligands. The lead compound 1-[4-methyl-3-(4-methyl piperazin-1-yl methyl) phenylsulfonyl]-1H-indole dihydrochloride ( 6b ), in this series, has shown potent in vitro binding affinity, selectivity, good pharmacokinetics (PK) profile and activity in the animal models of cognition.