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ID: ALA1147522

Journal: Bioorg Med Chem Lett

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

Authors: Chang-Fong J, Rangisetty JB, Dukat M, Setola V, Raffay T, Roth B, Glennon RA.

Abstract: An investigation of the structure-affinity relationships for the binding of 4-(N,N-dimethylaminomethyl)-N(9)-arylsulfonyl-9H-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)-9H-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 (pA(2)=7.0; cAMP hydrolysis assay).

CiteXplore: 15050637

DOI: 10.1016/j.bmcl.2004.01.071