Synthesis and antinociceptive activities of some novel benzimidazole-piperidine derivatives

Authors : ÜMİDE DEMİR ÖZKAY, ÖZGÜR DEVRİM CAN, NAZLI TURAN, Betül Kaya ÇAVUŞOĞLU

Pages : 672-684

View : 21 | Download : 14

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :In this study, a series of benzimidazole-piperidine derivatives were synthesized with the objective of developing potent antinociceptive agents. Some 2-insert ignore into journalissuearticles values(4-substituted-phenyl);-1-[2-insert ignore into journalissuearticles values(piperidin-1-yl);ethyl]-1$H$-benzimidazole derivatives were obtained by microwave-supported reaction of an appropriate 2-insert ignore into journalissuearticles values(4-substituted-phenyl);-1$H$-benzimidazole with 2-insert ignore into journalissuearticles values(piperidine-1-yl);ethyl chloride. The chemical structures of the compounds were elucidated by FT-IR, $^{1}$H NMR, $^{13}$C NMR, and HRMS spectral data. Antinociceptive activity was assessed by conducting hot-plate, paw-pressure, and formalin tests. Morphine insert ignore into journalissuearticles values(5 mg/kg, i.p); was used as a reference drug. Among the tested compounds 2a-2d and 2f-2h insert ignore into journalissuearticles values(10 mg/kg); increased the maximum possible effect insert ignore into journalissuearticles values(MPE); % values calculated for the hot-plate and paw-pressure tests and decreased the paw licking time of rats in the early phase of the formalin test, indicating centrally mediated antinociceptive activities of these derivatives. In the late-phase 2g and 2h were the only compounds reducing the paw licking duration. These data show additional peripherally mediated antinociceptive activities for these two derivatives. Falling latencies of animals in the rotarod test did not change upon the administration of test compounds; thus, the observed antinociceptive effects were specific. Predictions obtained by theoretical calculations of ADME insert ignore into journalissuearticles values(absorption, distribution, metabolism, excretion); properties supported the antinociceptive potential of the tested benzimidazole-piperidine derivatives.
Keywords : Benzimidazole, formalin test, hot plate test, paw pressure test, piperidine, rotarod