Synthesis and biological evaluation of novel γ-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists

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

“…The resulting activity was favorably compared with Dimebon I (Fig. 1) obtained following the method reported in our recent work [45]. Under normal conditions, HEK293 cells continuously produce recombinant human serotonin 5-HT 6 receptors.…”

“…1). The evaluated compounds of the general formula III are closely related in structure to compounds II, which have also been prepared recently and tested in vitro using a similar biological assay in our laboratory [45]. The overall aim of the present study is to investigate the spectrum of biological activity and selectivity of the title compounds against a panel of serotonin receptors as well as against histamine H 1 receptor.…”

8-Sulfonyl-substituted tetrahydro-1 H -pyrido[4,3- b ]indoles as 5-HT 6 receptor antagonists

“…It is being currently evaluated in advanced clinical trials as a promising small molecule drugcandidate for the treatment of Alzheimer's (Phase III) and Huntington's (Phase II) diseases [7]. Various pharmacological properties of dimebolin have been studied extensively [8][9][10][11][12]. Dimebolin possesses a remarkably broad spectrum of molecular target activity as well as a very complex mechanism of action, which allows one to consider it as an excellent example of a drug within the specific group of 'magic shotgun' drugs [13].…”

γ-Carboline AC190 analogues via palladium catalysed allene insertion stereo and regioselective 3- and 5-component cascades

“…Furthermore, a series of putative HDAC inhibitors bearing -and -carboline scaffolds has recently been patented for use as anti-cancer therapeutics by Grigg,10 with the most promising candidates being AC148 (5) and AC190 (6). An important requirement for biological activity within these systems appears to be the presence of a benzamide moiety, which is thought to bind to zinc ion present in the active site of the HDAC enzyme.…”