Design and Synthesis of Novel Core Scaffolds for the Development of Subtype Selective Estrogen Receptor Ligands

Abstract

The Estrogen Receptor (ER) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily which plays a crucial role in bone maintenance, cardiovascular function and reproductive processes in both men and women. Although the two subtypes of ER---ERalpha and ERbeta---share 96% homology in their DNA-binding domains, their ligand-binding domains share only 59% homology, allowing for the design of subtype-specific or selective estrogen receptor modulators commonly known as SERMs. We describe herein the design and synthesis of novel sulfonamide and spirocyclohexadienonyl systems for use as potential selective estrogen receptor modulators.