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Title: Structure-guided optimization of estrogen receptor binding affinity and antagonist potency of pyrazolopyrimidines with basic side chains.

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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); National Science Foundation (NSF)
OSTI Identifier:
936218
Report Number(s):
ANL/BIO/JA-61472
Journal ID: ISSN 0022-2623; JMCMAR; TRN: US200818%%596
DOE Contract Number:  
DE-AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Med. Chem.; Journal Volume: 50; Journal Issue: 2 ; 2007
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; AFFINITY; CHAINS; CRYSTAL STRUCTURE; ESTROGENS; FORECASTING; OPTIMIZATION

Citation Formats

Zhou, H., Sheng, S., Compton, D., Kim, Y., Joachimiak, A., Sharma, S., Carlson, K., Katzenellenbogen, B., Nettles, K., Greene, G., Katzenellenbogen, J., Biosciences Division, Univ. of Illinois, Univ. of Chicago, and The Scripps Research Inst. Structure-guided optimization of estrogen receptor binding affinity and antagonist potency of pyrazolopyrimidines with basic side chains.. United States: N. p., 2007. Web. doi:10.1021/jm061035y.
Zhou, H., Sheng, S., Compton, D., Kim, Y., Joachimiak, A., Sharma, S., Carlson, K., Katzenellenbogen, B., Nettles, K., Greene, G., Katzenellenbogen, J., Biosciences Division, Univ. of Illinois, Univ. of Chicago, & The Scripps Research Inst. Structure-guided optimization of estrogen receptor binding affinity and antagonist potency of pyrazolopyrimidines with basic side chains.. United States. doi:10.1021/jm061035y.
Zhou, H., Sheng, S., Compton, D., Kim, Y., Joachimiak, A., Sharma, S., Carlson, K., Katzenellenbogen, B., Nettles, K., Greene, G., Katzenellenbogen, J., Biosciences Division, Univ. of Illinois, Univ. of Chicago, and The Scripps Research Inst. Mon . "Structure-guided optimization of estrogen receptor binding affinity and antagonist potency of pyrazolopyrimidines with basic side chains.". United States. doi:10.1021/jm061035y.
@article{osti_936218,
title = {Structure-guided optimization of estrogen receptor binding affinity and antagonist potency of pyrazolopyrimidines with basic side chains.},
author = {Zhou, H. and Sheng, S. and Compton, D. and Kim, Y. and Joachimiak, A. and Sharma, S. and Carlson, K. and Katzenellenbogen, B. and Nettles, K. and Greene, G. and Katzenellenbogen, J. and Biosciences Division and Univ. of Illinois and Univ. of Chicago and The Scripps Research Inst.},
abstractNote = {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.},
doi = {10.1021/jm061035y},
journal = {J. Med. Chem.},
number = 2 ; 2007,
volume = 50,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}