biostudies-literatureSammeta VRU.S. Department of EnergySusan G. KomenU.S. Department of DefenseNorth Carolina Biotechnology Center1151-1158https://www.ebi.ac.uk/biostudies/studies/S-EPMC9290010biostudies-literatureUnknown13(7)Despite continued interest in the 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 α. 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.ACS medicinal chemistry lettersA New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core.PMC9290010CCR 19608597BC170954DE-AC02-06CH112572018-IDG-1030Fanning SWMcDonnell DPSammeta VRNorris JDArtham SWillson TMByemerwa JTorrice CDJoiner CfalseA New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core.Despite continued interest in the 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 α. 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.2022-01-01T00:00:00Z2022 Jul2026-05-28T01:28:28.427Z2024-11-21T05:43:27.093ZS-EPMC92900103585985910.1021/acsmedchemlett.2c00180