Synthesis and SAR study of modulators inhibiting tRXRα-dependent AKT activation
RXRα represents an intriguing and unique target for pharmacologic interventions. We recently showed that Sulindac and a designed analog could bind to RXRα and modulate its biological activity, including inhibition of the interaction of an N-terminally truncated RXRα (tRXRα) with the p85α regulatory subunit of phosphatidylinositol-3-OH kinase (PI3K). Here we report the synthesis, testing and SAR of a series of novel analogs of Sulindac as potential modulators for inhibiting tRXRα-dependent AKT activation. A new compound 30 was identified to have improved biological activity.
A facile one-pot conversion of acetates of the Baylis-Hillman adducts to [E]-α-methylcinnamic acids
A simple and convenient stereoselective synthesis of [E]-α- methylcinnamic acids via the nucleophilic addition of hydride ion from sodium borohydride to methyl 3-acetoxy-3-aryl-2-methylenepropanoates followed by hydrolysis and crystallization is described