Synthesis and Pharmacological Evaluation of Novel Benzimidazole Derivatives as Antiulcer and H+ K+ ATPase Inhibitor

Abstract

Aims: To Synthesis the novel substituted benzimidazole derivatives and screened Pharmacologically as antiulcer and H+ K+ ATPase inhibitor. Study Design: Study design as series of substituted benzimidazole derivatives prepared by three different reaction scheme and further evaluated pharmacologically in desired activity. Place and Duration of Study: In Patal Dhamal Wadwani College of Pharmacy Yavatmal, Maharashtra, India, between July 2014 to August 2017. Methodology: A series of new 2-[(substituted-pyrimidin-4-yl) sulfinyl]-1H-benzimidazole (54a-54i) were synthesized by the condensation of O-phenylenediamine, KOH and CS2 resulting potassium 1-H-benzimidazole 2-thiolate further treated with glacial acetic acid gives 1H-benzimidazole 2- thiol (2-mercaptobenzimidazole). 4-Chloro 2 Methyl, 6-Alkylpyrimidine- 4-ol prepared by ethanimidamide and alkyl acetoacetate gives 2-Methyl, 6-Alkylpyrimidine-4-ol by chlorination using thionyl chloride 4-Chloro 2 Methyl, 6-Alkylpyrimidine- 4-ol was obtained. further reacted with sodium oxide followed by m-chloroperbenzoic finally gives 2-[(substituted-pyrimidin-4-yl) sulfinyl]-1H-benzimidazole. Structural characterization of these synthesized compounds was confirmed by FT-IR, 1HNMR, and Mass spectral data. Later synthesized derivatives evaluated for their antiulcer and H+ K+ ATPase inhibitory activity by aspirin induced method and assays of H+/K+-ATPase activity respectively. Results: Compound 54c (74.03%), 54f (72.87%) and 54i (75.15%) shows highly significant antiulcer activity compared to standard drug and compound 54c (88.88 %), 54d (91.03 %), 54f (86.48%) and 54g (84.21%) shows highly significant antisecretory activity when compare to standard drug. Conclusion: Our research work provokes further to work for development of different derivatives of 2-(pyrimidinyl-sulfinyl) benzimidazole which have lesser side effect and better action than few of marketed drugs.