1. Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold
- Author
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Martinez, Claudio, Lieb, Michele, Rodriguez-Barrios, Fatima, Alvarez, Rosana, Khanwalkar, H., Gronemeyer, Hinrich, and de Lera, Angel R.
- Subjects
organic chemicals ,embryonic structures - Abstract
Arotinoids 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.
- Published
- 2014