Synthesis of some novel triazole derivatives as anti-nociceptive and anti-inflammatory agents

Aiyalu Rajasekaran, Kalasalingam Rajagopal
2009 Acta Pharmaceutica  
Tetrazole is a five-membered ring structure composed of four nitrogen atoms and one carbon atom and is used as an intermediate in the synthesis of pharmaceuticals, especially cephalosporins. Tetrazole and its derivatives have been reported to possess anti--nociceptive (1), anti-inflammatory (2), antimicrobial (3) and anticonvulsant properties (4, 5). Benzotriazole moiety is a versatile lead molecule in pharmaceutical development 355 Eight novel 1-[2-(1H-tetrazol-5-yl)ethyl]-1H-benzo[d][1,2,
more » ... H-benzo[d][1,2, 3]triazoles (3a-h) have been synthesized in order to obtain new compounds with potential anti-nociceptive and anti-inflammatory activity. The titled compounds were synthesized by the condensation of 1-[2-(1H-tetrazol-5-yl) ethyl]-1H-benzotriazole (2) and appropriate acid chlorides. Compound 2 was synthesized by reacting 3-(1H--benzo[d][1,2,3]triazol-1-yl)propanonitrile (1) with sodium azide and ammonium chloride in the presence of dimethylformamide. The synthesized compounds were characterized by spectroscopic methods (IR, 1 H NMR, mass spectroscopy) and elemental analysis. The titled compounds were evaluated for anti-nociceptive activity by the hot plate method and the writhing response method, and anti-inflammatory activity was evaluated by the carragenean induced paw edema method. 5-(2-(1H-benzo[d][1,2,3] triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(4-aminophenyl)methanone (3d) and 5-(2-(1H-benzo[d][1,2,3]triazo-1-yl)ethyl)--1H-tetrazol-1-yl)(2-hydroxyphenyl)methanone (3g) exhibited significant anti-nociceptive activity. 1-(2-(1-Tosyl--1H-tetrazol-5-yl)ethyl)-1H-benzo[d][1,2,3]triazole (3c) and 4,5-(2-(1H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl sulfonyl)benzenamine (3f) elicited superior anti-inflammatory activity compared to other synthesized compounds. Further investigations are needed to discern the mechanism of action. and has a wide range of biological activities, e.g., anti-inflammatory (6), anti-nociceptive (7), anticonvulsant (8), antimicrobial (9), protein kinase inhibiting (10) and immunosuppressive activities (11). Our research was focused on incorporation of the benzotriazole moiety into tetrazoles based upon the hypothesis that this modification would improve efficacy, since both moieties are noted for their anti-nociceptive and anti-inflammatory properties. Thus, a series of novel 1-[2-(1H-tetrazol-5-yl)ethyl]-1H-benzo[d][1,2,3]triazoles were synthesized and tested for their anti-nociceptive and anti-inflammatory properties. EXPERIMENTAL Melting points were determined using a melting point apparatus (Veego, VMP III, India) and were not corrected. Infrared spectra were obtained on a Perkin Elmer FTIR spectrophotometer 1600 series (Perkin Elmer, USA) using potassium bromide discs. 1 H NMR spectra were recorded on a Bruker 400 MHz spectrophotometer (Bruker, USA). Chemical shifts are reported in parts per million (d) units relative to an internal standard 356 A. Rajasekaran and K. A. Rajagopal: Synthesis of some novel triazole derivatives as anti-nociceptive and anti-inflammatory agents, Acta Pharm. 59 (2009) 355-364.
doi:10.2478/v10007-009-0026-7 pmid:19819831 fatcat:m7fuo5l4i5bphlqr6d7y6imzf4