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A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core.

Publication ,  Journal Article
Sammeta, VR; Norris, JD; Artham, S; Torrice, CD; Byemerwa, J; Joiner, C; Fanning, SW; McDonnell, DP; Willson, TM
Published in: ACS Med Chem Lett
July 14, 2022

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.

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Published In

ACS Med Chem Lett

DOI

ISSN

1948-5875

Publication Date

July 14, 2022

Volume

13

Issue

7

Start / End Page

1151 / 1158

Location

United States

Related Subject Headings

  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0305 Organic Chemistry
  • 0304 Medicinal and Biomolecular Chemistry
 

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Sammeta, V. R., Norris, J. D., Artham, S., Torrice, C. D., Byemerwa, J., Joiner, C., … Willson, T. M. (2022). A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core. ACS Med Chem Lett, 13(7), 1151–1158. https://doi.org/10.1021/acsmedchemlett.2c00180
Sammeta, Vamshikrishna Reddy, John D. Norris, Sandeep Artham, Chad D. Torrice, Jovita Byemerwa, Carstyn Joiner, Sean W. Fanning, Donald P. McDonnell, and Timothy M. Willson. “A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core.ACS Med Chem Lett 13, no. 7 (July 14, 2022): 1151–58. https://doi.org/10.1021/acsmedchemlett.2c00180.
Sammeta VR, Norris JD, Artham S, Torrice CD, Byemerwa J, Joiner C, et al. A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core. ACS Med Chem Lett. 2022 Jul 14;13(7):1151–8.
Sammeta, Vamshikrishna Reddy, et al. “A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core.ACS Med Chem Lett, vol. 13, no. 7, July 2022, pp. 1151–58. Pubmed, doi:10.1021/acsmedchemlett.2c00180.
Sammeta VR, Norris JD, Artham S, Torrice CD, Byemerwa J, Joiner C, Fanning SW, McDonnell DP, Willson TM. A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core. ACS Med Chem Lett. 2022 Jul 14;13(7):1151–1158.
Journal cover image

Published In

ACS Med Chem Lett

DOI

ISSN

1948-5875

Publication Date

July 14, 2022

Volume

13

Issue

7

Start / End Page

1151 / 1158

Location

United States

Related Subject Headings

  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0305 Organic Chemistry
  • 0304 Medicinal and Biomolecular Chemistry