Structure-activity relationships of retinoids in hamster tracheal organ culture.
Structure-activity relationships are summarized for 87 retinoids, using reversal of keratinization in the hamster tracheal organ culture system to measure biological activity. Classes of compounds evaluated include all-trans-retinoic acid and its esters, ring-modified analogs of all-trans-retinoic acid and its esters, side-chain-modified analogs of all-trans-retinoic acid and its esters, analogs in which both ring and side chain have been modified, all-trans-retinol and derivatives, all-trans-retinyl amine derivatives, all-trans-retinal derivatives, all-trans-retinoic acid amides, 13-cis-retinoic acid and derivatives, and 5,6-epoxyretinoids. the activity of many synthetic amide derivatives of all-trans- or 13-cis-retinoic acid approaches that of the parent compounds. No metabolite of all-trans- or 13-cis-retinoic acid has yet been identified which has greater activity than the parent compounds in this assay. New synthetic derivatives with a gem-dimethyl group at position 4 in the cyclohexenyl ring and two aromatic rings in the side chain have activity equal to or greater than that of all-trans- or 13-cis-retinoic acid, with some activity detectable in the 10(-11) M range.
D000818:Animals; D006224:Cricetinae; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007633:Keratins / Q000096:biosynthesis; D009924:Organ Culture Techniques; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects*; D014212:Tretinoin / Q000031:analogs & derivatives*
D014212:Tretinoin; D007633:Keratins