title: 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-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).
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Chang-Fong
authors.forename: Jagadeesh B
authors.initials: JB
authors.lastname: Rangisetty
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dukat
authors.forename: Vincent
authors.initials: V
authors.lastname: Setola
authors.forename: Thomas
authors.initials: T
authors.lastname: Raffay
authors.forename: Bryan
authors.initials: B
authors.lastname: Roth
authors.forename: Richard A
authors.initials: RA
authors.lastname: Glennon
mesh_terms: D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002227:Carbazoles; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; C409925:1,2,3,4-tetrahydrocarbazole