Identification of a chromone-based retinoid containing a polyolefinic side chain via facile synthetic routes.
Attempts to prepare substituted chromones as novel retinoids revealed that some chromones were unstable under Wadsworth-Horner-Emmons reaction conditions. Hence, Wittig reactions were used to prepare chromone-based compounds as potential retinoids. Firstly, Wittig reagents prepared from 3-bromomethyl-chromen-4-one were reacted with olefinic-aldehydes to provide the target compounds with all-trans side chains in good yield. The approach supplies a useful general route to structurally diverse chromone-based compounds possessing a variety of side chains. Sequential Wittig reactions were used also to prepare a chromone-based retinoid. These novel compounds were evaluated in binding assays and a high affinity RAR ligand was identified. Crystal structures obtained for two key precursors aided the interpretation of binding data.
Sun
Weilin
W
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Carroll
Patrick J
PJ
Soprano
Dianne R
DR
Canney
Daniel J
DJ
D000447:Aldehydes / Q000737:chemistry; D000077556:Alitretinoin; D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D012176:Retinoids / Q000737:chemistry*; D014212:Tretinoin / Q000737:chemistry
D000447:Aldehydes; D000475:Alkenes; D000970:Antineoplastic Agents; D008024:Ligands; D012176:Retinoids; D000077556:Alitretinoin; D014212:Tretinoin