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bioRxiv · 10.1101/2022.04.15.488344

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

Sammeta, V. R.·Norris, J. D.·Artham, S.·Torrice, C. D.·Byemerwa, J.·Joiner, C.·Fanning, S. W.·McDonnell, D. P.·Willson, T. M.
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Abstract

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

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Sammeta, V. R., Norris, J. D., Artham, S., Torrice, C. D., Byemerwa, J., Joiner, C., Fanning, S. W., McDonnell, D. P., Willson, T. M.. 2022-04-15. A new chemotype of chemically tractable nonsteroidal estrogens based on a thienopyrimidine core.. https://doi.org/10.1101/2022.04.15.488344

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