85554-28-5Relevant articles and documents
Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptors
Sikazwe, Donald,Bondarev, Mikhail L.,Dukat, Ma?gorzata,Rangisetty, Jagadeesh B.,Roth, Bryan L.,Glennon, Richard A.
, p. 5217 - 5225 (2007/10/03)
Various sulfonyl-containing compounds (e.g. sulfonamides, sulfones) bind at human 5-HT6 serotonin receptors, but it has been difficult relating the binding mode(s) of such agents to one another, even though many possess a common SO2 moiety, to identify a common pharmacophore model(s). On the basis of the hypothesis that an ergoline-type conformation might be important for the binding of some sulfonamide-containing arylalkylamines, we prepared for examination at h5-HT6 receptors a series of compounds, including phenylethylamines 6, pyrroloethylamine 7, and phenylpiperazines 9. The results (with Ki values ranging from about 1 nM to > 1000 nM) suggest that many of these agents likely bind in a related fashion, and structure-affinity studies indicate that the benzenesulfonamide portion of the phenylethylamine and phenylpiperazine analogues can be "reversed", abbreviated to a sulfone, and moved to an adjacent position with relatively little impact on affinity. Although a benzenesulfonamide (or related arylsulfonamide) group might be common to various 5-HT6 ligands, there appears to be some latitude with regard to the specific constitution and location of the sulfonamide moiety even within the same arylalkylamine structural framework. A pharmacophore model is presented to account for some of the current findings.
