A new chemotype of chemically tractable nonsteroidal estrogens based on a thienopyrimidine core.

Despite continued interest in development of nonsteroidal estrogens and antiestrogens, there are only a few chemotypes of estrogen receptor ligands. Using targeted screening in a ligand sensing assay we identified a phenolic thieno[2,3-d]pyrimidine with affinity for estrogen receptor . An efficient three-step synthesis of the heterocyclic core and structure-guided optimization of the substituents resulted in a series of potent nonsteroidal estrogens. The chemical tractability of the thieno[2,3-d]pyrimidine chemotype will support the design of new estrogen receptor ligands as therapeutic hormones and antihormones. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=48 SRC="FIGDIR/small/488344v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@4a0c18org.highwire.dtl.DTLVardef@16001f5org.highwire.dtl.DTLVardef@20a58forg.highwire.dtl.DTLVardef@1558bdf_HPS_FORMAT_FIGEXP M_FIG C_FIG