Synthesis and Biological Evaluation of Novel 5,8‐Disubstituted‐2‐methyl‐2,3,4,5‐tetrahydro‐1H‐pyrido[4,3‐b] indoles as 5‐HT6 and H1 Receptors Antagonists

Synthesis, biological evaluation, and structure‐activity relationships (SAR) for a series of novel γ‐carboline analogues of Dimebon are described. Among the studied compounds, tetrahydro‐γ‐carboline 5b (2,8‐dimethyl‐5‐[cis‐2‐pyridin‐3‐ylvinyl]‐2,3,4,5‐tetrahydro‐carboline) has been identified as the most potent small molecule antagonist, in particular against histamine H₁ and serotonin 5‐HT₆ receptors (IC₅₀ < 0.45 μM and IC₅₀ = 0.73 μM, respectively). A thorough comparative SAR study performed for the tested compounds has revealed significant correlations between the nature of side substituents and the related antagonistic activity.