NONSTEROIDAL GLUCOCORTICOID-LIKE SUBSTANCES - RECEPTOR-BINDING AND IN-VIVO ACTIVITY

Compounds of general structure I, prepared by a Diels-Alder reaction w ith diene 3, are relatives of the known potent glucocorticoid II but p ossess a markedly modified C- and D-ring environment. Despite these st ructural changes, 4, 5, 9, 10, 12a, 13, and 14 bound to the glucocorti coid receptor with an affinity which approximated that of the referenc e standard, 6-alpha-methylprednisolone. Four of these compounds not on ly exhibited antiinflammatory activity in the alpha-tocopherol pouch t est but also exhibited marked adrenal suppression and other typical gl ucocorticoid properties at doses in the same range as the effective an tiinflammatory doses.