Solid-Phase Combinatorial Approach to Estradiol Tamoxifen/Raloxifene Hybrids: Novel Chemotherapeutic/Prophylactic Selective Estrogen Receptor Modulators (SERM).

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. During the past year we have functionalized the carboxy resin with both the E-and Z-tributylstannylvinyl estradiol. We have prepared and characterized the initial series of iodophenoxyalkylamines that will be coupled to the resin-bound steroid. The biological assays have been established and validated using series of previously prepared compounds. Molecular modeling and NMR spectrometric methods for conformational analyses and for data analysis have been developed. The next years specific aims involve the synthesis and evaluation of the initial series of target compounds.