Available online at www.pelagiaresearchlibrary.com Pelagia Research Library Der Chemica Sinica, 2017, 8(1):168-181 ISSN : 0976-8505 CODEN (USA): CSHIA5 Pelagia Research Library 168 Anti-Infammatory, Proton Pump Inhibitor and Synthesis of Some New Benzimidazole Derivatives Rezk R Ayyad 1,5 , Helmi M Sakr 1 , Kamal M El-Gamal 2,4* , Ibrahim H Eissa 1 , Ahmad HA Tita 1 , Adel S Abd El-Raheim 1 , Farag F Sherbini 2 and Ahmad M Mansour 3 1 Pharmaceutical Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt 2 Organic Chemistry Department, Al-Azher University (Boys), Nasser City, Cairo, Egypt 3 Pharmacology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt 4 Organic Chemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Gammsa, Egypt 5 Medicinal Chemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Gammsa, Egypt ABSTRACT A series of novel of 1 and 2-substituted benzimidazoles was synthesized by the reaction of Phenelenediamine with p-hydroxybenzaldehyde. All the synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, and elemental analysis. The newly benzimidazoles derivatives were screened for analgesic and anti-infammatory activities on carrageenan induced paw oedema in rats. Among all the benzimidazol derivatives, compound 8b and 10 exhibited signifcant analgesic and anti-infammatory activities. Acute ulcerogenicity studies showed that compound 6 did not cause any gastric mucosal lesions in the rat stomach at the dose (300 mg/kg) indicating that this compound is devoid of gastric irritant properties. Keywords: Benzimidazole, Anti-infammatory, Proton pump inhibitor, Docking Abbreviation: M.P: Melting Point; DMF: Dimethyl Formamide; TLC: Thin Layer Chromatography; DMSO: Dimethyl Sulfoxide; CDCl 3 : Deuterated Chloroform INTRODUCTION The cause of infammation includes physical agents, chemical agents, immunological reactions, and infection by a pathogenic organism [1]. Nonsteroidal anti-infammatory drugs (NSAIDs) are one of the most widely used drug categories against infammation, mild to moderate pain and fever this is essentially brought about by inhibiting the rate limiting cyclooxygenase (COX) enzyme involved in the infammatory cascade [2]. However, long term medication of NSAIDs is associated with adverse effects like hepatotoxicity, platelet dysfunction and bleeding [3,4]. But the major side effect is gastrointestinal (GI) ulcerations due to inhibition of cyclooxygenase (COX) in tissues exerted with chronic use of NSAIDs. Consequently, a real need exists to develop new anti-infammatory, analgesic effect with good effcacy, fewer toxicity and less side effects of gastric ulceration. Herein we need to discovery and development of novel anti-infammatory and analgesic agents along with safety profle is still a necessity. On synthesizing novel chemical modifcations or derivatization of existing benzimidazole moieties could lead to neutral molecules with greatly reduced acidic ulceration as a useful approach to explore safer and potent anti-infammatory and analgesic agent [5]. Among different types of NSAIDs, Benzimidazole [6] which is a structural unit of naturally occurring nucleotide, because it easily interacts with the biopolymers of living systems [7] and due to this character it responsible for its numerous biological aspects like anthelmintic [8], antifungal [9], antimicrobial [10,11], antiviral [12] and antineoplastic [13] activities. The aforesaid different pharmacological activities of benzimidazoles encouraged us to study the in-vivo analgesic and anti-infammatory activities of some important new 1. 2 substituted benzimidazole derivatives aiming at fnding new gastroprotective leads with potential anti-infammatory, analgesic activities. In the present research work, a novel series of 1, 2-substituted benzimidazole derivatives have been synthesized and bio- evaluated for their anti-infammatory, analgesic, and allergenic activity of the resulted compounds. The non-steroidal anti-infammatory drugs become main COX inhibitors.