Kumar V, Bell M R, Wetzel J R, Herrmann J L, McGarry R, Schane H P, Winneker R C, Snyder B W, Anzalone A J
Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania 19426-0900.
J Med Chem. 1993 Oct 29;36(22):3278-85. doi: 10.1021/jm00074a008.
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.
