Synthesis and antiinflammatory and analgesic activity of 5-aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-ca rboxyl ic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids.
5-Aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carb oxylic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids were synthesized and assayed as antiinflammatory and analgesic agents. The majority of these compounds exhibit a surprisingly low level of antiinflammatory activity (rat carrageenan paw) but have considerable potency as analgesics (mouse phenylquinone writing). For example, the p-tolyl-substituted bicyclic and monocyclic compounds 44 and 58 are 301 and 66 times more potent than aspirin (mouse writhing) but only 3.4 and 1.5 times more potent than phenylbutazone in the antiinflammatory screen (rat paw).
Muchowski
J M
JM
Syntex Research, Institute of Organic Chemistry, Palo Alto, California 94304.
Galeazzi
E
E
Greenhouse
R
R
Guzmán
A
A
Peréz
V
V
Ackerman
N
N
Ballaron
S A
SA
Rovito
J R
JR
Tomolonis
A J
AJ
Young
J M
JM
D000085:Acetates / Q000138:chemical synthesis / Q000627:therapeutic use; D000698:Analgesia; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D016227:Benzoquinones; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000627:therapeutic use; D002351:Carrageenan; D055598:Chemical Phenomena; D002621:Chemistry; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D010147:Pain Measurement; D010653:Phenylbutazone / Q000627:therapeutic use; D011758:Pyrroles / Q000138:chemical synthesis / Q000627:therapeutic use; D011809:Quinones; D051381:Rats
D000085:Acetates; D016227:Benzoquinones; D002264:Carboxylic Acids; D011758:Pyrroles; D011809:Quinones; C029322:phenylbenzoquinone; D002351:Carrageenan; D010653:Phenylbutazone; D001241:Aspirin