Synthesis of Tetrazoloquinoline-Based Mono- and Bisphosphonate Esters as Potent Anti-Inflammatory Agents

Several new a-alkoxy- and a-hydroxyphosphonate derivatives of tetrazole-quinolines were synthesized from the reaction of 2-azidoquinolines 3-carboxaldehyde 1a,b with trialkyl phosphites and dialkyl phosphites. On the other hand, azaphospholes 12a,b were obtained by treating 1a,b with tris(dimethylamino)phosphine. Furthermore, Perkin-type condensation of 1a,b and tetraethyl methylenebisphosphonate provided the corresponding tetrazoloquinoline-based bisphosphonate esters 14a,b. Based on the prediction results (PASS program), the anti-inflammatory activity of the prepared compounds was determined in vivo by the acute carrageenin-induced paw edema in rats. Many of the new compounds exhibit considerable anti-inflammatory properties at a dose of 50 mg/kg body weight. Especially 14a and 14b revealed remarkable activities compared with indomethacin, which was used as a reference standard in this study.