10.1016/j.bmcl.2009.11.037
The research presents the synthesis and biological evaluation of novel 5-styryl and 5-phenethyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, which are analogs of the drug dimebolin. The study focuses on the synthesis of these compounds and their activity against therapeutically relevant targets, such as serotonergic, adrenergic, histamine, and other receptors. The experiments involved the reaction of aryl acetylenes with tetrahydro-1H-c-carbolines in a biphasic system using DMSO, KOH, and a phase-transfer catalyst, leading to the formation of (Z)- and (E)-isomers of 2-methyl-5-styryl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles. Further hydrogenation yielded the desired 5-phenethyl derivatives. The structures of the compounds were confirmed using LC–MS and 1H NMR spectroscopy, with specific attention to the chemical shifts and coupling constants indicative of the (Z)- and (E)-isomers. The biological activities were assessed through cell-based assays, measuring the compounds' abilities to inhibit serotonin-induced responses, block histamine H1 receptors, and their affinities to various receptors, which were determined by displacement of radio-labeled ligands. The most potent compounds were further profiled against a panel of 31 therapeutic targets to determine their specificity.
10.1080/00304948.2015.1025017
The study details the synthesis of Latrepirdine (also known as Dimebon) and its tetrathiomolybdate derivative. Dimebon is an antihistamine drug with potential cognitive-enhancing and neuroprotective properties, particularly in Alzheimer’s and Huntington’s disease models. The researchers developed a reproducible process to prepare Dimebon starting from methyl 6-methylnicotinate, involving several steps including reduction, condensation, and nitrosation, ultimately leading to the final product via the Fischer Indole Synthesis. The study also explores the synthesis of dimebon tetrathiomolybdate, a compound that combines dimebon's neuroprotective properties with the copper-complexing abilities of the tetrathiomolybdate ion, which has been shown to lower insoluble beta-amyloid levels in Alzheimer's disease models. Two methods for preparing the tetrathiomolybdate derivative were investigated, with the first yielding the product in 82% yield. The study provides detailed procedures and characterizations of the synthesized compounds, highlighting their potential medicinal applications.
