Synthesis and anti-inflammatory activity of polyazaheterocyclic derivatives of 6-amino-2,4-lutidine and their precursors.
Derivatives of N-(4,6-pyridin-2-yl)arylcarboxamides resulting from the integration of the amidic function into 4H-1,2,4-triazole, triazol-3(2H)-one and 1H-tetrazole rings were evaluated as potential anti-inflammatory compounds. The level of activity decreased as compared to carboxamides, nevertheless their precursors and notably the corresponding amidrazones exhibited potent activity; amidrazone 21, whose ID50 was 34.4 mg.kg-1 in the rat paw edema test, was selected for further investigation. These heteroarylcarboxamide derivatives could represent an interesting alternative to classical non-steroidal anti-inflammatories in so far as they partly act by inhibition of tumor necrosis factor-alpha production.
Robert
J M
JM
Laboratoires de Chimie Organique et Chimie Thérapeutique, Faculté de Pharmacie, Nantes, France.
Rideau
O
O
Robert-Piessard
S
S
Duflos
M
M
Le Baut
G
G
Grimaud
N
N
Juge
M
M
Petit
J Y
JY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007928:Lethal Dose 50; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011725:Pyridines; D013777:Tetrazoles; D014230:Triazoles; C078448:2,4-dimethylpyridine; D002351:Carrageenan