Document Report Card

ID: ALA1145074

Journal: J Med Chem

Title: Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors.

Authors: Khorana N, Smith C, Herrick-Davis K, Purohit A, Teitler M, Grella B, Dukat M, Glennon RA.

Abstract: On the basis of an earlier finding that 5-methyl-5H-1,2,3,4-tetrahydropyrido[4,3-b]indole (5-methyl-1,2,3,4-tetrahydro-gamma-carboline; 1) binds at murine 5-HT(5A) receptors, preliminary structure-affinity studies were conducted. The present investigation extends these structure-affinity studies using human 5-HT(5A) receptors and examined additional analogues of 1. It was found (a) that there is little interspecies difference for the affinities of these compounds, (b) that an intact 1,2,3,4-tetrahydro-gamma-carboline ring system seems optimal and an N(2)-(3-(substituted-phenoxy)propyl) moiety results in high affinity, (c) that structurally related 1,2,3,4-tetrahydro-beta-carbolines also bind at 5-HT(5A) receptors, and (d) that all examined derivatives also possess affinity for 5-HT(2A) receptors. Evidence is provided that 5-HT(5A) and 5-HT(2A) receptor affinities probably do not covary and that it might be possible, with continued investigation, to develop analogues with enhanced 5-HT(5A) selectivity.

CiteXplore: 12930153

DOI: 10.1021/jm030080s