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Synthesis and antinociceptive activities of some novel benzimidazole-piperidine derivatives

In this study, a series of benzimidazole-piperidine derivatives were synthesized with the objective of developing potent antinociceptive agents. Some 2-(4-substituted-phenyl)-1-[2-(piperidin-1-yl)ethyl]-1H-benzimidazole derivatives were obtained by microwave-supported reaction of an appropriate 2-(4-substituted-phenyl)-1H-benzimidazole with 2-(piperidine-1-yl)ethyl chloride. The chemical structures of the compounds were elucidated by FT-IR, 1H NMR, 13C NMR, and HRMS spectral data. Antinociceptive activity was assessed by conducting hot-plate, paw-pressure, and formalin tests. Morphine (5 mg/kg, i.p) was used as a reference drug. | Turkish Journal of Chemistry Turk J Chem 2017 41 672 684 http journals.tubitak.gov.tr chem ITAK c TUB Research Article doi 10.3906 kim-1612-76 Synthesis and antinociceptive activities of some novel benzimidazole-piperidine derivatives Umide DEMIR OZKAY 1 ur Devrim CAN1 Nazlı TURAN1 Bet Ozg ul KAYA C AVUS OGLU 2 1 Department of Pharmacology Faculty of Pharmacy Anadolu University Eski sehir Turkey 2 Department of Pharmaceutical Chemistry Faculty of Pharmacy Anadolu University Eski sehir Turkey Received 27.12.2016 Accepted Published Online 29.03.2017 Final Version 10.11.2017 Abstract In this study a series of benzimidazole-piperidine derivatives were synthesized with the objective of developing potent antinociceptive agents. Some 2- 4-substituted-phenyl -1- 2- piperidin-1-yl ethyl -1 H -benzimidazole derivatives were obtained by microwave-supported reaction of an appropriate 2- 4-substituted-phenyl -1 H -benzimidazole with 2- 1 13 piperidine-1-yl ethyl chloride. The chemical structures of the compounds were elucidated by FT-IR H NMR C NMR and HRMS spectral data. Antinociceptive activity was assessed by conducting hot-plate paw-pressure and formalin tests. Morphine 5 mg kg i.p was used as a reference drug. Among the tested compounds 2a 2d and 2f 2h 10 mg kg increased the maximum possible effect 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 absorption distribution metabolism excretion .