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

• Published in: Journal of heterocyclic chemistry Vol. 50; no. 1; pp. 33 - 41
• Main Authors: Abdou, Wafaa M., Khidre, Rizk E., Shaddy, Abeer A.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Blackwell Publishing Ltd 01.01.2013; Wiley; Wiley Subscription Services, Inc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; EFFICIENT SYNTHESIS; CHEMISTRY; CARRAGEENAN; PHOSPHOR ESTERS
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.968

Several new α‐alkoxy‐ and α‐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.