Solid Phase Combinatorial Approach to Estradiol Tamoxifen/Raloxifene Hybrids: Novel Chemotherapeutic/Prophylactic Selective Estrogen Receptor Modulators

摘要

The objective of this project is the development of new chemotherapeutic agents for the treatment of hormone-responsive breast cancer using a solid phase approach to synthesize new agents having features common to both steroids and antiestrogens. Previously we functionalized the carboxy resin with both the E-and Z-tributylstannylvinyl estradiol, and prepared an initial series of iodophenoxyalkylamines that will be coupled to the resin-bound steroid. Coupling reactions with the Z-stannylvinyl estradiol were generally unsuccessful on solid-phase and coupling with the E-isomers proceeded in low yields. We have prepared more iodophenoxyalkylamines and are preparing the target compounds via solution phase methods. We are exploring an approach using resin-bound estradiol vinylboronic acids as an alternative method.