Synthesis of carboxyalkylthio-triazoles and bicyclic derivatives with antiinflammatory and analgesic activity.
3-Carboxyalkylthio derivatives of 5-alkoxyphenyl-1,2,4-triazole were prepared, performing some substitutions both on carboxyalkyl chain, by lengthening it or introducing substituents with increasing molecular weight in alpha- at the carboxy group, and on N-4 atom in the triazole ring, by introducing an amino or methyl group, so that to vary steric conformation along with the lipophilicity of molecules. The corresponding bicyclic thiazolo-triazolone and triazolo-thiazinone derivatives, which represent the rigid models of carboxymethylthio- and carboxyethylthio- open structures, were also obtained. All the compounds show "in vivo" antiinflammatory activity, while only carboxyalkylthio derivatives of 4-amino- and 4-methyltriazole display an appreciable analgesic one. From the relief of some data on substituent present in the synthesized compounds, a structure-activity relationship is also suggested.
Mazzone
G
G
Istituto di Chimica Farmaceutica e Tossicologica, Italy.
Pignatello
R
R
Mazzone
S
S
Panico
A
A
Barbera
F
F
Catti
T
T
Chiechio
S
S
Arrigo-Reina
R
R
Castorina
C
C
Russo
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007928:Lethal Dose 50; D051379:Mice; D010147:Pain Measurement; D051381:Rats; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013844:Thiazoles; D014230:Triazoles; D013481:Superoxides; D002351:Carrageenan