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Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold
journal contribution
posted on 2014-05-08, 00:00 authored by Claudio Martínez, Michele Lieb, Susana Álvarez, Fátima Rodríguez-Barrios, Rosana Álvarez, Harshal Khanwalkar, Hinrich Gronemeyer, Angel R. de LeraArotinoids containing a C5,C8-diphenylnaphthalene-2-yl
ring linked
to a (C3-halogenated) benzoic acid via an ethenyl connector (but not
the corresponding naphthamides), which are prepared by Horner–Wadsworth–Emmons
reaction of naphthaldehydes and benzylphosphonates, display the rather
unusual property of being RXR agonists (15-fold induction of the RXR
reporter cell line was achieved at 3- to 10-fold lower concentration
than 9-cis-retinoic acid) and RAR antagonists as
shown by transient transactivation studies. The binding of such bulky
ligands suggests that the RXR ligand-binding domain is endowed with
some degree of structural elasticity.