Work

Structure-Guided Optimization of Estrogen Receptor Binding Affinity and Antagonist Potency of Pyrazolopyrimidines with Basic Side Chains

Year: 2006

Type: article

Abstract: 2,3-Diarylpyrazolo[1,5-a]pyrimidines are estrogen receptor (ER) antagonists of modest potency that we have described previously. Guided by the crystal structure of an ER-ligand complex that we have obtained with one of these compounds, we prepared analogs that contain a basic side chain at the 2- or 3-aryl group and quickly found one that, according to the structure-based prediction, shows an increase in binding affinity and antagonist potency and a loss of residual agonist activity.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm061035y

Authors: Hai-Bing Zhou, Shubin Sheng, Dennis R. Compton, Younchang Kim, Andrzej Joachimiak, Sanjay Sharma, Kathryn E. Carlson, Benita S. Katzenellenbogen, Kendall W. Nettles, Geoffrey L. Greene, John A. Katzenellenbogen

Institutions: Argonne National Laboratory, University of Illinois Urbana-Champaign, University of Illinois Chicago, University of Chicago

Language: English

Topic: Estrogen and related hormone effects

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Medical Research and Materiel Command

Awards: Development and Characterization of Novel SERMs, G1637269988, G4976532050, G6308123614

OpenAlex ID: W2003446299

FWCI: 1.59

Cites: 36

Cited by: 43

Related to: 10