Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor-coactivator interaction

Jong Yeon Hwang; Ramy R. Attia; Angela K. Carrillo; Michele C. Connelly; R. Kiplin Guy

doi:10.1016/j.bmcl.2012.12.055

Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor-coactivator interaction

Jong Yeon Hwang
, Ramy R. Attia
, Angela K. Carrillo
, Michele C. Connelly
, R. Kiplin Guy

Producción científica: Article › revisión exhaustiva

6 Citas (Scopus)

Resumen

We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which replace the ester linkage of MSNBs with a thiazole, also inhibited coactivator binding to TR. Here we report that replacement of the ester with an amide (methylsulfonylnitrobenzamides, MSNBA) also provides active TR antagonists.

Idioma original	English
Páginas (desde-hasta)	1891-1895
Número de páginas	5
Publicación	Bioorganic and Medicinal Chemistry Letters
Volumen	23
N.º	6
DOI	https://doi.org/10.1016/j.bmcl.2012.12.055
Estado	Published - mar 15 2013

Nota bibliográfica

Funding Information:
This work was supported by NIH/NIAID (Grant Al075517 , DK58080 ), the American Lebanese Syrian Associated Charities (ALSAC), and St. Jude Children’s Research Hospital.

Financiación

This work was supported by NIH/NIAID (Grant Al075517 , DK58080 ), the American Lebanese Syrian Associated Charities (ALSAC), and St. Jude Children’s Research Hospital.

Financiadores	Número del financiador
NIH-NIAID	Al075517
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK058080
St. Jude Children's Research Hospital
American Lebanese Syrian Associated Charities

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2012.12.055

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title = "Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor-coactivator interaction",

abstract = "We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which replace the ester linkage of MSNBs with a thiazole, also inhibited coactivator binding to TR. Here we report that replacement of the ester with an amide (methylsulfonylnitrobenzamides, MSNBA) also provides active TR antagonists.",

keywords = "Coactivator, Inhibitor, Protein interaction, Thyroid",

author = "Hwang, \{Jong Yeon\} and Attia, \{Ramy R.\} and Carrillo, \{Angela K.\} and Connelly, \{Michele C.\} and Guy, \{R. Kiplin\}",

note = "Funding Information: This work was supported by NIH/NIAID (Grant Al075517 , DK58080 ), the American Lebanese Syrian Associated Charities (ALSAC), and St. Jude Children{\textquoteright}s Research Hospital. ",

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doi = "10.1016/j.bmcl.2012.12.055",

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AU - Hwang, Jong Yeon

AU - Attia, Ramy R.

AU - Carrillo, Angela K.

AU - Connelly, Michele C.

AU - Guy, R. Kiplin

N1 - Funding Information: This work was supported by NIH/NIAID (Grant Al075517 , DK58080 ), the American Lebanese Syrian Associated Charities (ALSAC), and St. Jude Children’s Research Hospital.

PY - 2013/3/15

Y1 - 2013/3/15

N2 - We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which replace the ester linkage of MSNBs with a thiazole, also inhibited coactivator binding to TR. Here we report that replacement of the ester with an amide (methylsulfonylnitrobenzamides, MSNBA) also provides active TR antagonists.

AB - We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which replace the ester linkage of MSNBs with a thiazole, also inhibited coactivator binding to TR. Here we report that replacement of the ester with an amide (methylsulfonylnitrobenzamides, MSNBA) also provides active TR antagonists.

KW - Coactivator

KW - Inhibitor

KW - Protein interaction

KW - Thyroid

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DO - 10.1016/j.bmcl.2012.12.055

M3 - Article

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor-coactivator interaction

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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