Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring

Bryan H. Norman; Timothy I. Richardson; Jeffrey A. Dodge; Lance A. Pfeifer; Gregory L. Durst; Yong Wang; Jim D. Durbin; Venkatesh Krishnan; Sean R. Dinn; Shengquan Liu; John E. Reilly; Kendal T. Ryter

doi:10.1016/j.bmcl.2007.07.009

Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring

Bryan H. Norman
, Timothy I. Richardson
, Jeffrey A. Dodge
, Lance A. Pfeifer
, Gregory L. Durst
, Yong Wang
, Jim D. Durbin
, Venkatesh Krishnan
, Sean R. Dinn
, Shengquan Liu
, John E. Reilly
, Kendal T. Ryter

Center for Translational Medicine

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Benzopyrans are selective estrogen receptor (ER) β agonists (SERBAs), which bind the ER receptor subtypes α and β in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERα, thus improving ERβ subtype selectivity. X-ray cocrystal structures with ERα and ERβ are supportive of this approach to improve selectivity in this structural class.

Original language	English
Pages (from-to)	5082-5085
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2007.07.009
State	Published - Sep 15 2007

Keywords

Crystallography
Estrogen receptor β
Prostate

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10.1016/j.bmcl.2007.07.009

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Norman, B. H., Richardson, T. I., Dodge, J. A., Pfeifer, L. A., Durst, G. L., Wang, Y., Durbin, J. D., Krishnan, V., Dinn, S. R., Liu, S., Reilly, J. E., & Ryter, K. T. (2007). Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring. Bioorganic and Medicinal Chemistry Letters, 17(18), 5082-5085. https://doi.org/10.1016/j.bmcl.2007.07.009

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title = "Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring",

abstract = "Benzopyrans are selective estrogen receptor (ER) β agonists (SERBAs), which bind the ER receptor subtypes α and β in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERα, thus improving ERβ subtype selectivity. X-ray cocrystal structures with ERα and ERβ are supportive of this approach to improve selectivity in this structural class.",

keywords = "Crystallography, Estrogen receptor β, Prostate",

author = "Norman, \{Bryan H.\} and Richardson, \{Timothy I.\} and Dodge, \{Jeffrey A.\} and Pfeifer, \{Lance A.\} and Durst, \{Gregory L.\} and Yong Wang and Durbin, \{Jim D.\} and Venkatesh Krishnan and Dinn, \{Sean R.\} and Shengquan Liu and Reilly, \{John E.\} and Ryter, \{Kendal T.\}",

year = "2007",

month = sep,

day = "15",

doi = "10.1016/j.bmcl.2007.07.009",

language = "English",

volume = "17",

pages = "5082--5085",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Norman, BH, Richardson, TI, Dodge, JA, Pfeifer, LA, Durst, GL, Wang, Y, Durbin, JD, Krishnan, V, Dinn, SR, Liu, S, Reilly, JE & Ryter, KT 2007, 'Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 18, pp. 5082-5085. https://doi.org/10.1016/j.bmcl.2007.07.009

TY - JOUR

T1 - Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4

T2 - Functionalization of the benzopyran A-ring

AU - Norman, Bryan H.

AU - Richardson, Timothy I.

AU - Dodge, Jeffrey A.

AU - Pfeifer, Lance A.

AU - Durst, Gregory L.

AU - Wang, Yong

AU - Durbin, Jim D.

AU - Krishnan, Venkatesh

AU - Dinn, Sean R.

AU - Liu, Shengquan

AU - Reilly, John E.

AU - Ryter, Kendal T.

PY - 2007/9/15

Y1 - 2007/9/15

N2 - Benzopyrans are selective estrogen receptor (ER) β agonists (SERBAs), which bind the ER receptor subtypes α and β in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERα, thus improving ERβ subtype selectivity. X-ray cocrystal structures with ERα and ERβ are supportive of this approach to improve selectivity in this structural class.

AB - Benzopyrans are selective estrogen receptor (ER) β agonists (SERBAs), which bind the ER receptor subtypes α and β in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERα, thus improving ERβ subtype selectivity. X-ray cocrystal structures with ERα and ERβ are supportive of this approach to improve selectivity in this structural class.

KW - Crystallography

KW - Estrogen receptor β

KW - Prostate

UR - https://www.scopus.com/pages/publications/34547914087

U2 - 10.1016/j.bmcl.2007.07.009

DO - 10.1016/j.bmcl.2007.07.009

M3 - Article

C2 - 17662603

AN - SCOPUS:34547914087

SN - 0960-894X

VL - 17

SP - 5082

EP - 5085

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

Benzopyrans as selective estrogen receptor β agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring

Abstract

Keywords

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