Antiinflammatory 4,5-diarylpyrroles: synthesis and QSAR.
A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in the rat adjuvant arthritis model of inflammation. The most active compounds were the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity relationship studies suggested that the activity could be correlated with the molar refractivity and the inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent.
Wilkerson
W W
WW
Du Pont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0353.
Galbraith
W
W
Gans-Brangs
K
K
Grubb
M
M
Hewes
W E
WE
Jaffee
B
B
Kenney
J P
JP
Kerr
J
J
Wong
N
N
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D004195:Disease Models, Animal; D004361:Drug Tolerance; D008297:Male; D011758:Pyrroles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011758:Pyrroles