Cyanobiphenyls: Novel H3 receptor ligands with cholinesterase and MAO B inhibitory activity as multitarget compounds for potential treatment of Alzheimer’s disease

Dual Piperidine-Based Histamine H3 and Sigma-1 Receptor Ligands in the Treatment of Nociceptive and Neuropathic Pain

“…The synthesis of the desired final compounds 1−16 was achieved through the synthetic route presented in Scheme 1. According to the previously described procedure, 19,21,22,24,25 the phenoxy alkyl bromides a−i were obtained mainly by one-step alkylation of commercially available phenols with 1,3-dibromopropane (a−e), 1,4dibromobutane (f, i), 1,5-dibromopentane (g), or 1,6dibromohexane (h) in propan-1-ol under reflux conditions. Obtained precursor bromides were then coupled with 3methylpiperidine (1), 4-methylpiperidine (2), azepane (3), pyrrolidine (4), piperidine (5−11), 4-(piperidin-4-yl)pyridine (12−15), or 2-(piperazin-1-yl)pyrazine (16) in a mixture of ethanol/water with powdered potassium carbonate and a catalytic amount of potassium iodide.…”

“… a Data published in ref . b Recalculated from data published in ref . c Data published in ref . d Data published in ref . e Data published in ref . f Given data represent mean values within the 95% confidence interval (CI). …”

“…Compounds 5, 10, 11, and 16 were obtained as in previous studies and used in the biological assays with high purity estimated using LC/MS; details of their synthesis and analyses are described elsewhere. 19,24,25 4.1. (16).…”

“…All compounds were obtained using methods described previously. ,,,, To a suspension of potassium carbonate (8.5 mmol) and a catalytic amount of potassium iodide in water (10 mL), a mixture of proper amine (5 mmol) and compound a – i (5 mmol) in ethanol (50 mL) was added as previously described. ,,,, The mixture was then refluxed for 8–12 h (TLC controlled). After cooling down to room temperature, reaction mixture was filtrated, evaporated, and purified.…”

“…All compounds were obtained using methods described previously. ,,,, To a solution of freshly prepared sodium 1-propanolate (0.1 mol, 100 mL), proper substituted phenols (0.1 mol) were added and stirred in room temperature for 5 min. α,ω-Dibromoalkanes (0.2 mol) were then added dropwise in the time of 1 h. The reaction mixture was stirred in 60 °C for 3 h and then refluxed for another 3 h. After cooling down to RT, the mixture was filtrated and evaporated.…”