Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities

Invention Patent: <B> "SYNTHESIS AND USE OF RETINOID COMPOUNDS WITH NEGATIVE HORMONE ACTIVITIES AND / OR ANTAGONISTS" <D>. Derivatives of the type benzopyran, benzothiopyran, 1,2-dihydroquinoline and 5,6-dihydronaphthalene substituted with aryl and with aryl and (3-oxo-1-propenyl) have biological activities of the negative hormone and / or retinoid antagonist type. The invented RAR antagonists can be administered to mammals, including humans, in order to prevent or decrease the action of RAR agonists at the bound receptor sites. Specifically, RAR agonists are administered or co-administered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or precursors to vitamin A. negative retinoid hormones can be used to enhance the activities of other retinoids and nuclear receptor agonists. For example, the negative retinoid hormone called AGN 193109 has effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays.In addition, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors constructed to possess a constitutive transcription activating domain.