Synthesis, Characterization and Screening for Analgesic and Anti-inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives.
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.
Department of Pharmaceutical Chemistry, Rungta College of Pharmaceutical Sciences and Research, Bhilai, 490024, Chhattisgarh, India. danu_drugs@yahoo.com.
Dhansay
D
Dewangan
Kartik T
KT
Nakhate
D K
DK
Tripathi
Pranita
P
Kashyap
Hemant
H
Dhongde
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010069:Oxadiazoles