*Corresponding Author Address: B. Vishwanathan, Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Sri Shivarathreeshwara Nagar, Mysore, Karnataka-570 015, India; E-mail: vishwanathan_b@yahoo.co.in World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Original Article Anticoagulant evaluation of 1,3,4-oxadiazole derivatives derived from benzimidazole B. Vishwanathan*and B.M. Gurupadayya Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Sri Shivarathreeshwara Nagar, Mysore, Karnataka-570 015, India Received: 22-11-2014 / Revised: 31-12-2014 / Accepted: 02-01-2015 Abstract In the present study, a series of 1,3,4-oxadiazole derivatives (4a-4k) derived from benzimidazole were evaluated for ex vivo anticoagulant activity. The anticoagulant study was performed for increase in prothrombin time (PT) and activated partial thromboplastin time (aPTT) at a test dose of 25 mg kg -1 . The results of ex vivo anticoagulant evaluation revealed that the tested compounds 4a-4k exhibited moderate increase in PT with respect to acenocoumarol (1 mg kg -1 ) employed as reference drug for increase in PT. While the compounds 4a- 4k exhibited minimal increase in aPTT in comparison to unfractionated heparin (500 IU kg -1 ) employed as reference drug for increase in aPTT. Compounds, 4c, 4b and 4k exhibited substantial anticoagulant activity with increase in PT 32 ± 0.7, 36 ± 0.5 and 41 ± 0.4 s, respectively to that of the reference drug acenocoumarol (48 ± 0.5 s). Keywords: 1,3,4-Oxadiazole; Activated Partial Thromboplastin Time; Benzimidazole; Prothrombin Time. INTRODUCTION The lacunae in present medication for management of arterial thromboembolism (ATE) disorders by anticoagulant therapy are having recurrent ATE episodes. ATE is the most common cause of cardioembolic events including myocardial infarction, ischemic stroke, and limb gangrene. ATE is currently the leading cause of death and illness in developed countries, principal causes of morbidity and mortality world-wide.[1] Clinical studies highlight that anticoagulants are the drugs of choice for the prevention and treatment of ATE disorders, and prophylaxis of thrombotic events in both pre- and post-surgery in clinical practices.[2] Warfarin, acenocoumarol and phenprocoumon which are the major 4-hydroxycoumarin derivatives presently available in clinical use as oral anticoagulants have been the core of anticoagulantion therapy for more than two decades.[3] Generally known as antivitamin K, pharmacological 4-hydroxycoumarin anticoagulants are vitamin K epoxide reductase (VKOR) inhibitors. Vitamin K is converted to its active form by the enzyme VKOR and recycled to vitamin K 2,3-epoxide to maintain the coagulation cycle.[4] 4-hydroxycoumarin derivatives like warfarin, acenocoumarol and phenprocoumon antagonize VKOR, thus preventing vitamin K recycling and resulting in an accumulation of abnormal form of coagulation protein, known as proteins induced by vitamin K antagonism or des- Ȗ-carboxyprothrombin leading to inhibition of the coagulation process. The narrow therapeutic index and other major clinical drawbacks like drug-drug interaction, food-drug interaction, purple toe syndrome, eclampsia, risk of haemorrhage etc., call for continuous therapeutic drug monitoring for 4- hydroxycoumarin anticoagulants. These entire therapeutic shortcomings indicate the need for better anticoagulant agents with clinical advantage. In our previous study, we had reported the synthesis and characterization of 1,3,4-oxadiaozle derivatives 4a-4k (Fig. 1), from (1H- benzo[d]imidazol-2-yl)methanamine.[5] Wherein, N-[(1H-benzo[d]imidazol-2-yl)methyl](5- substituted-1,3,4-oxadiazol-2-yl)methanamine; 4a- 4j (Table 1) were prepared by nucleophilic addition of aryl/heteroaryl/aliphatic carboxylic acids with 2- [(1H-benzo[d]imidazol-2-yl) methylamino] acetohydrazide in presence of phosphorous oxychloride. The acetohydrazide derivative was prepared by condensation of ethyl 2-[(1H- benzo[d]imidazol-2-yl)methylamino]acetate with hydrazine monohydrate. The ester derivative was prepared by N-alkylation of (1H-benzo[d]imidazol- 2-yl)methanamine with ethyl 2-chloroacetate in the presence of anhydrous potassium carbonate. The