Pak. J. Pharm. Sci., Vol.26, No.2, March 2013, pp.345-352 345 Synthesis, characterization and biological screening of 5- substituted-1,3,4-oxadiazole-2yl-N-(2-methoxy-5-chlorophenyl)- 2-sulfanyl acetamide Aziz-ur-Rehman 1 *, Ambreen Fatima 1 , Nadia Abbas 1 , Muhammad Athar Abbasi 1 , Khalid Mohammed Khan 2 , Muhammad Ashraf 3 , Irshad Ahmad 4 and Syeda Abida Ejaz 4 1 Department of Chemistry, Government College University, Lahore, Pakistan 2 HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan 3 Department of Biochemistry and Biotechnology; 4 Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan Abstract: In the current study, a series of 5-substituted-1,3,4-oxadiazole-2yl-N-(2-methoxy-5-chlorophenyl)-2-sulfanyl acetamide was synthesized by converting variously substituted/unsubstituted aromatic organic acids successively into the corresponding esters, hydrazides and then 5-substituted-1,3,4-oxadiazole-2-thiols. Finally the target compounds were obtained by stirring 5-substituted-1,3,4-oxadiazole-2-thiols with N-(2-methoxy-5-chlorophenyl)-2-bromoacetamide in the presence of N,N-dimethyl formamide (DMF) and sodium hydride (NaH). The structures of the synthesized compounds were confirmed based on 1 H-NMR, IR and mass spectral data. The synthesized compounds were screened against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase enzymes (LOX) and were found to be relatively more active against acetyl cholinesterase. Keywords: Aromatic acids; oxadiazoles; acetylcholinesterase; 1 H-NMR and EI-MS. INTRODUCTION 1,3,4-oxadiazoles belong to the group of compounds that have been made a center of attention for last two decades due to their broad range of biological activities. Some of them exhibit anticonvulsant, antibacterial, anticancer activities and are used to fight infections involving AIDS. 2,5-disubstituted-1,3,4-oxadiazoles have been reported to have significant activities like antidepressive (Piala et al., 1964), anticonvulsive (Almasirad et al., 2004), analgesic (Angilini et al., 1969), herbicidal (Kennedy et al., 1981), muscle relaxant (Yale et al., 1966), pesticidal (Ram et al., 1988), anti-malarial agents (Bahadur et al., 1980), antitumor as well as anti-HCV agents (Rostom et al., 2003). Due to the appealing biological activity of 2,5- disubstituted 1,3,4-oxadiazole, an extensive concentration has been focused on this group. The significance of these compounds lies in the fact that they can be successfully utilized as antibacterial, analgesic, anti-inflammatory, anticancer, anti-HIV agent, anti-tubercular and insecticidal agents (Boschelli et al., 1993; Cansız et al., 2004; Koparır et al., 2005; Hemavathi et al., 2011 and Kumar, 2011). Literature survey revealed that minor modification in the structure of substituted 1,3,4- oxadiazole can lead to quantitative as well as qualitative changes in the biological activity. Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) consist of an enzymes family which includes serine hydrolases. The diverse specificities for the substrates and inhibitors for these enzymes are due to the dissimilarity in amino acid remains of the active sites of AChE and BChE. Actually the system of enzyme is responsible for the termination of acetylcholine at cholinergic synapses. These are key components of cholinergic brain synapses and neuromuscular junctions. The central function of AChE and BChE is to catalyze the hydrolysis of the neurotransmitter acetylcholine and termination of the nerve impulse in cholinergic synapses (Cygler et al., 1993 and Tougu, 2001). It has been found that BChE is present in appreciably higher quantity in Alzheimer's plaques than in the normal age linked dementia of brains. H 1 and H 2 receptor antagonists possess AChE inhibitory activities. Cholinesterase inhibitors raise the quantity of acetylcholine available for neuronal and neuromuscular transmission through their ability to reversibly or irreversibly. Hence, the search for new cholinesterase inhibitors is considered an important and ongoing strategy to introduce new drug candidates for the treatment of Alzheimer’s disease and other related diseases (Bertaccini 1982 and Gauthier 2001). This paper reports the synthesis and biological screening of some new 5-substituted-1,3,4-oxadiazole-2-sulfanyl acetamide with the objective of having lesser toxicity and enhanced activity of the synthesized compounds. In continuation of our previous work (Rehman et al., 2012), the synthesis was carried out through the intermolecular cyclization of different substituted/unsubstituted organic *Corresponding author: e-mail: azizryk@yahoo.com