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

Bioorg Med Chem Lett. 2004 Apr 19;14(8):1961-4. doi: 10.1016/j.bmcl.2004.01.071.

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).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Humans
  • Ligands
  • Molecular Structure
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Carbazoles
  • Ligands
  • Receptors, Serotonin
  • Serotonin Antagonists
  • serotonin 6 receptor
  • 1,2,3,4-tetrahydrocarbazole