Adult, albino rats of the Charles River strain, 100 days of age, weighing 190–210 gm, were bilaterally ovariectomized, and 1 week later were placed on experiments to ascertain the influence of Δ1, 9α fluoro-17-hydroxycorticosterone (ΔFF) on estradiol-17ß-induced uterine growth. The results indicate that ΔFF when administered in a daily dosage up to 0.20 mg for 3 days did not modify the weight of the uterus of the ovariectomized rat, whereas 3 daily dosages of 0.10 µg estradiol-17ß effected an increase of approximately 85% in uterine weight. When 0.05–0.20 mg ΔFF was injected daily, but at different sites, with 0.10 µg estradiol-17ß for the 3-day period, the response of the uterus to estradiol-17ß was markedly reduced from the estradiol-17ß-induced increase of 85% to 52% on the lowest dosage of ΔFF down to 24% on the highest dose (0.20 mg) of ΔFF. These experiments further indicate that the inhibition of estradiol-17ß-induced uterine growth could be partially reversed by increasing the dosage of estradiol-17ß. Comparatively, data at hand suggest that ΔFF > 9αFlF > compound F > compound E > Δ1E and Δ1F in inhibiting 0.10 µg estradiol-17ß on the uterus and the vagina of the ovariectomized rat. Moreover, the incorporation of an additional double bond in ring A (Δ1) and flourine atom in the 9α position of compound F enhances the uterine growth inhibiting activity of compound F. Of the numerous glucocorticoids and mineralocorticoids tested for ability to inhibit estradiol-17ß, ΔFF is by far the most efficacious.
Syntheses of 2-(6’-Fluorobenzothiazol-2’-ylamino)-4, 6-(disubstituted thiouriedo)-1,3-pyrimidine Derivatives as Antimicrobial Agents
