Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

Xiaoyuan Li; Ellyn Shocron; Aimin Song; Neela Patel; Connie L. Sun

doi:10.1016/j.bmcl.2009.03.074

Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

Xiaoyuan Li, Ellyn Shocron, Aimin Song, Neela Patel, Connie L. Sun^*

^*Corresponding author for this work

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

8 Citations (Scopus)

Abstract

A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 μM. The structure-activity relationship (SAR) of this series is reported here.

Original language	English
Pages (from-to)	2860-2864
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2009.03.074
Publication status	Published - 15 May 2009
Externally published	Yes

Keywords

Hsp90 inhibitors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2009.03.074

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@article{40fb95bd0e574dafaf3670b4da9e7008,

title = "Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors",

abstract = "A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 μM. The structure-activity relationship (SAR) of this series is reported here.",

keywords = "Hsp90 inhibitors",

author = "Xiaoyuan Li and Ellyn Shocron and Aimin Song and Neela Patel and Sun, \{Connie L.\}",

year = "2009",

month = may,

day = "15",

doi = "10.1016/j.bmcl.2009.03.074",

language = "English",

volume = "19",

pages = "2860--2864",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "10",

}

Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors. / Li, Xiaoyuan; Shocron, Ellyn; Song, Aimin et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 10, 15.05.2009, p. 2860-2864.

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

TY - JOUR

T1 - Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

AU - Li, Xiaoyuan

AU - Shocron, Ellyn

AU - Song, Aimin

AU - Patel, Neela

AU - Sun, Connie L.

PY - 2009/5/15

Y1 - 2009/5/15

N2 - A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 μM. The structure-activity relationship (SAR) of this series is reported here.

AB - A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 μM. The structure-activity relationship (SAR) of this series is reported here.

KW - Hsp90 inhibitors

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000265627800056

UR - https://openalex.org/W2034155525

UR - https://www.scopus.com/pages/publications/65349183594

U2 - 10.1016/j.bmcl.2009.03.074

DO - 10.1016/j.bmcl.2009.03.074

M3 - Journal Article

SN - 0960-894X

VL - 19

SP - 2860

EP - 2864

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 10

ER -

Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

Abstract

Keywords

UN SDGs

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