1,2,3,4-tetrahydrocarbazoles as 5-HT6 serotonin receptor ligands.

Abstract An investigation of the structure–affinity relationships for the binding of 4-( N , N -dimethylaminomethyl)-N 9 -arylsulfonyl-9 H -1,2,3,4-tetrahydrocarbazoles (conformationally-constrained analogues of the benzenesulfonyltryptamine 5-HT 6 antagonist MS-245) at human 5-HT 6 receptors revealed that various arylsulfonyl substituents are tolerated and that the 4-( N , N -dimethylaminomethyl) group is not required for binding. In particular, N 9 -(4-aminobenzenesulfonyl)-9 H -1,2,3,4-tetrahydrocarbazole ( 20 , K i =29 nM) was found to bind with high affinity and represents the first member of a new structural class of agents with 5-HT 6 antagonist properties (p A 2 =7.0; cAMP hydrolysis assay).