| abstract |
ryl-substituted and aryl and (3-oxo-1-propenyl)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives of the formula 1 where X is S, O, NR' where R' is H or alkyl of 1-6 carbons R1 is H or alkyl of 1-6 carbons R2 is H, lower alkyl, F, Cl, Br, I, CF3, fluoro substituted alkyl of 1-6 carbons, OH, SH, alkoxy or 1-6 carbons, or alkylthio of 1-6 carbons R3 is H, lower alkyl of 1-6 carbons or F m is 0-3 o is 0-3 Z is C=C, N=N, N=CR1, CR1=N and other groups Y is phenyl or naphthyl or heteroaryl A is (CH2)q where q is 0-5, lower branched chain alkyl , cycloalkyl, alkenyl, alkynyl B is H, COOH and other carbon oxygen groups which have retinoid negative hormone and/or antagonist-like biological activities. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, 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 engineered to possess a constitutive transcription activator domain. Divisional filed as 500397 |