Non-steroidal glucocorticoid-like substances: receptor binding and in vivo activity.
Compounds of general structure I, prepared by a Diels-Alder reaction with diene 3, are relatives of the known potent glucocorticoid II but possess a markedly modified C- and D-ring environment. Despite these structural changes, 4, 5, 9, 10, 12a, 13, and 14 bound to the glucocorticoid receptor with an affinity which approximated that of the reference standard, 6-alpha-methylprednisolone. Four of these compounds not only exhibited antiinflammatory activity in the alpha-tocopherol pouch test but also exhibited marked adrenal suppression and other typical glucocorticoid properties at doses in the same range as the effective antiinflammatory doses.
Kumar
V
V
Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania 19426-0900.
Bell
M R
MR
Wetzel
J R
JR
Herrmann
J L
JL
McGarry
R
R
Schane
H P
HP
Winneker
R C
RC
Snyder
B W
BW
Anzalone
A J
AJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D005938:Glucocorticoids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011720:Pyrazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D011720:Pyrazoles; D011965:Receptors, Glucocorticoid