Synthesis, Characterization and Screening for Analgesic and Anti-inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives

Abstract

The aim of the present investigation was to synthesize, characterize and evaluate analgesic and anti- inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives. The reaction of starting material 4-chloro-m-cresol with ethyl chloroacetate in dry acetone affords ethyl (4-chloro-3-methylphenoxy) acetate, which after reacting with the hydrazine hydrate in ethanol yields 2(4-chloro-3-methylphenoxy) acetohydrazide. When 2(4-chloro-3-methylphenoxy) acetohydrazide was treated with different aromatic aldehydes, aromatic acids and carbon disulfide in alcoholic solution, different 3-acetyl-5-[(4-chloro-3-methylphenoxy) methyl]-2-aryl-2, 3-dihydro-1, 3, 4-oxadiazole and 2-[(4-chloro-3-methylphenoxy) methyl]-5-aryl-1, 3, 4-oxadiazole derivatives were obtained. Purity of the derivatives was confirmed by thin layer chromatography and melting point. Structure of these derivatives was set up by determining infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy. Further, the synthesized derivatives were evaluated for their analgesic and anti-inflammatory activities in rodents. In animal studies, the derivatives 3-acetyl-5-[(4-chloro-3- methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole and 4-{5-[(4-chloro-3- methylphenoxy)methyl]-1, 3, 4-oxadiazol-2-yl}pyridine show more potent analgesic activity and the derivatives 2-{3-acetyl-5-[(4-chloro-3-methylphenoxy)methyl]-2,3-dihydro-1, 3, 4-oxadiazol-2-yl}phenol and 3-acetyl-5- [(4-chloro-3-methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole exhibit more potent anti-inflammatory effect as compared to other derivatives. The results of the current study indicate that cyclization of acetohydrazide produces novel oxadiazole derivatives with potent analgesic and anti-inflammatory activities.

Synthesis, Characterization, and Screening for Analgesic and Anti‐Inflammatory Activities of Schiff Bases of 1,3,4‐Oxadiazoles Linked With Quinazolin‐4‐One

“…In our recent study, we observed analgesic and anti‐inflammatory activities of 1,3,4‐oxadiazole derivatives . Further, we linked 1,3,4‐oxadiazole with quinazolin‐4‐one moieties and noticed significant analgesic and anti‐inflammatory activities as compared with 1,3,4‐oxadiazole derivatives .…”

“…Therefore, we have attempted to develop the derivatives of oxadiazole nucleus at 2‐position and 5‐postion with a view to evaluate further the potency of the molecules. In our previous study , we have synthesized 1,3,4‐oxadiazole derivatives. These agents produced up to 47% inhibition of acetic acid‐induced writhing reflex and up to 41% inhibition of carrageenan‐induced paw edema.…”

Analgesic and Anti‐inflammatory Potential of Merged Pharmacophore Containing 1,2,4‐triazoles and Substituted Benzyl Groups via Thio Linkage

“…The analgesic activity was performed according to the protocol given by Dewangan et al . Animals were randomly divided into three groups: (A) Control [acetic acid treated ( n = 6)], (B) 1,2,4‐triazole derivatives + acetic acid treated ( n = 6) and (C) Acetyl salicylic acid + acetic acid treated ( n = 6).…”

A Review on the Preparation of 1,3,4-Oxadiazoles From the Dehydration of Hydrazines and Study of Their Biological Roles

“…Synthesis of 1,3,4-oxadiazole containing compounds and investigation of their chemical and biological properties has accelerated in recent years. 1,3,4-Oxadiazole represents an important class of biologically active species which exhibits antibacterial [1], antibiotic [2], antiviral [3], anti inflammatory [4], pesticidal [5], antiallergic [6], analgesic [7,8], ocular hypotensive [9], antimalarial [10], anticancer [11,12], anticonvulsant [13,14], antitumor [15][16][17], herbicidal [18], angiogenesis inhibitor [19], antiedema [20], anti obesity [21], antioxidant [22], anti-infective [23], anti HIV [24], antiparasitic [25], antihyperglycemic [26], anxiolytic [27],antidepressant [28], antiproliferative [29], antiplatelet [30] and gastric antisecretory activities [31]. Most of the drugs which are available in the market contains 1,3,4-oxadiazole unit.…”