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SUMMARY Although the ACTH-suppressing, eosinopenic,and hyperglycemic activities of corticosteroids havepreviously been considered to be inseparable,three synthetic cortisol analogues have been foundto exhibit significant degrees of dissociation among these biological activities. These three com- poundswere1) 9a-fluoro-1 lf8,17a-dihydroxy-A1' 4-pregnene-3,20-dione; 2) 9a,21-difluoro-11/8,17a- dihydroxy-A4-pregnene-3,20-dione; and 3) 6a-methyl-9a-fluoro-1 1,3,17-dihydroxy-Al 4-pregnene-3,20-dione-21-mesylate. When compared with9a-fluoro-1 1,3,17a,21-trihydroxy-z1" 4-pregnene-3,-20-dione as a biological standard, all three of theabove steroids werefound to be somewhatless ef-fective as ACTH-suppressing agents, but almosttotally ineffective as eosinopenic and hyperglyce-micagents. Thedegree of dissociation of ACTH-suppressing activity from eosinopenic and hyper-glycemic activities became greater as dosage wasincreased and was statistically significant at thehigher dosage levels for each of the three steroids.

DISSOCIATION OF CORTICOTROPIN-SUPPRESSING ACTIVITY FROM THE EOSINOPENIC AND HYPERGLYCEMIC ACTIVITIES OF CORTICOSTEROID ANALOGUES*