A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3- d ]pyrimidine Core
Year: 2022
Type: article
Abstract: 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 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. GRAPHICAL ABSTRACT
Source: ACS Medicinal Chemistry Letters
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Energy, Pfizer, North Carolina Biotechnology Center, Loyola University Chicago, Genome Canada, Susan G. Komen, Merck KGaA, European Federation of Pharmaceutical Industries and Associations, Ontario Ministry of Economic Development and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministero dello Sviluppo Economico, Genentech, Novartis Pharma, Biological and Environmental Research, Argonne National Laboratory
OpenAlex ID: W4281608252