Tanaproget

A combination of all the effects rendering agonistic activity resulted in the discovery of tanaproget (44). The compound was clinically investigated until phase III, but its development was stopped at this stage (Scheme 6.15). 

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. 

In a recent study, the bicydic core of tanaproget was changed to a p-(5-cyano-pyrrol-2-yl) substituted aniline scaffold that was decorated at the aniline by combinatorial chemistry approaches. Most promising compounds carried a small sulfonamide at the aniline and competitive receptor binding with an ICS0=1.5nM has been reported (Scheme 6.16). 

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