Tanaproget and Related Structures

PRE-Luc transactivation assay in CV1 cells it was antagonistic with an IC50 of 6.7 nM. This antagonistic effect was confirmed in an in vivo decidualization assay. 

The activity of compound 41 was reversed to agonism by changing the carbonyl group into a thiocarbonyl group (42). Compound 42 was agonistic in vitro with a potency in the alkaline phosphatase assay of 0.7 nM. 

The bicyclic benzoxazine-2-thione core of tanaproget was replaced by several other systems like an indolone or a 2-thioloindole (45), resulting in activity in the same dose range like MPA in a decidualization assay. 

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