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2q70

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==Overview==
==Overview==
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Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here, we describe the syntheses of cyclopentanone and cyclohexanone, intermediates for SAR studies of the C-ring on the benzopyran scaffold., Modification of the C-ring disrupts binding to ERalpha, thus improving, ERbeta selectivity up to 100-fold. X-ray cocrystal structures confirm, previously observed binding modes.
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Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the syntheses of cyclopentanone and cyclohexanone intermediates for SAR studies of the C-ring on the benzopyran scaffold. Modification of the C-ring disrupts binding to ERalpha, thus improving ERbeta selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes.
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==Disease==
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Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]]
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: Synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification., Richardson TI, Dodge JA, Durst GL, Pfeifer LA, Shah J, Wang Y, Durbin JD, Krishnan V, Norman BH, Bioorg Med Chem Lett. 2007 Sep 1;17(17):4824-8. Epub 2007 Jun 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17614275 17614275]
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Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification., Richardson TI, Dodge JA, Durst GL, Pfeifer LA, Shah J, Wang Y, Durbin JD, Krishnan V, Norman BH, Bioorg Med Chem Lett. 2007 Sep 1;17(17):4824-8. Epub 2007 Jun 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17614275 17614275]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: transcription factor]]
[[Category: transcription factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:34:21 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:41 2008''

Revision as of 16:36, 21 February 2008


2q70, resolution 1.95Å

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Estrogen receptor alpha ligand-binding domain complxed to a benzopyran ligand

Contents

Overview

Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the syntheses of cyclopentanone and cyclohexanone intermediates for SAR studies of the C-ring on the benzopyran scaffold. Modification of the C-ring disrupts binding to ERalpha, thus improving ERbeta selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes.

Disease

Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]

About this Structure

2Q70 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification., Richardson TI, Dodge JA, Durst GL, Pfeifer LA, Shah J, Wang Y, Durbin JD, Krishnan V, Norman BH, Bioorg Med Chem Lett. 2007 Sep 1;17(17):4824-8. Epub 2007 Jun 20. PMID:17614275

Page seeded by OCA on Thu Feb 21 18:36:41 2008

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