Discovery of pimozide derivatives as novel T-type calcium channel inhibitors with little binding affinity to dopamine D2 receptors for treatment of somatic and visceral pain

A new synthetic approach to cyclic ureas through carbonylation using di-tert-butyl dicarbonate (boc anhydride) via one pot strategy

“…Yield 1.1 g, 75%, 1 3.1.7. Synthesis of 5-bromo-4′-methoxy-N 3 -methyl-[1,1′biphenyl]-2,3-diamine (7). A solution of 6-bromo-4-(4-methoxyphenyl)benzo[c][1,2,5]selenadiazole (6) (1.1 g, 2.97 mmol) in dimethyl sulphate (4.5 mL) was stirred at 130 °C for 1 h. The reaction mixture was cooled to RT, washed with diethyl ether (2 × 20 mL) to remove excesses of dimethyl sulphate and to the resulted solid was added 2 N NaOH solution (10 mL).…”

“…The reaction mixture was stirred at RT vigorously for 1 h. The reaction mixture was extracted with ethyl acetate (100 mL), the organic layer was dried over sodium sulfate and concentrated under reduced pressure. The resulted crude was purified by column chromatography (silica gel; 100-200 mesh: 15% ethyl acetate in petroleum ether as eluent) to afford the 0.6 g of title compound (7). Red solid.…”

“…Urea motifs, particularly when incorporated into molecular frameworks, have demonstrated enhanced biological activities. In the last few years, benzimidazole and benzimidazolone have been studied extensively for their antipsychotic, 7 anti-allergic, 8 neuroleptic, 9 antitumor, antiviral, antihypertensive and antibiotic activity. 10 Noteworthy instances include the urea linkage within the tankyrase inhibitor, 11 the BCL6 Inhibitor, 12 and the natural product Kealiiquinone.…”

Dietary Zinc Deficiency Induces Ca_v3.2-Dependent Nociceptive Hypersensitivity in Mice

“…2,3) In the mammalian body, the activity of Ca v 3.2 channels is suppressed by zinc that binds to a histidine residue at a position 191 present on the extracellular domain of Ca v 3.2, and, therefore, can be enhanced by various compounds with a high affinity to zinc, such as L-cysteine 4,5) and hydrogen sulfide (H 2 S), an endogenous gaseous mediator. 3,[6][7][8][9][10] Actually, intrathecal (i.t. ), intraplantar (i.pl.)…”