Design, synthesis and pharmacological evaluation of indolylsulfonamide amines as potent and selective 5-HT₆receptor antagonists

Abstract

A series of N 0 -[3-(indole-1-sulfonyl) aryl]-N,N-dimethyl ethane-1,2-diamines and N 0 -[3-(indole-1-sulfonyl) aryl]-N,N-dimethyl propane-1,3-diamines was designed and synthesized as 5-HT 6 receptor ligands. These compounds, when screened in a functional reporter gene-based assay, displayed potent antagonistic activity with K b values in the range of 1.8-60 nM. The lead compound 9y has shown good ADME surrogate properties, acceptable pharmacokinetic profile and is active in animal models of cognition like novel object recognition test and Morris water maze. It was selected for detailed profiling.

Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives

“…The data are the means ± SEM of at least 5 separate experiments, and the final pA 2 values are obtained from the linear regression of Schild plot. 27…”