The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Michele C Connelly - One of the best experts on this subject based on the ideXlab platform.
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synthesis and evaluation of methylsulfonylnitrobenzamides msnbas as inhibitors of the thyroid hormone receptor coactivator interaction
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Jong Yeon Hwang, Ramy R Attia, Angela K Carrillo, Michele C ConnellyAbstract: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.
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synthesis and evaluation of sulfonylnitrophenylthiazoles snpts as thyroid hormone receptor coactivator interaction inhibitors
Journal of Medicinal Chemistry, 2012Co-Authors: Jong Yeon Hwang, Ramy R Attia, Lei Yang, Andrew S Lemoff, Cynthia Jeffries, Michele C ConnellyAbstract:We previously identified a series of methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its coactivators. MSNBs inhibit coactivator binding through irreversible modification of cysteine 298 of the thyroid hormone receptor (TR). Although MSNBs have better pharmacological features than our first generation inhibitors (β-aminoketones), they contain a potentially unstable Ester Linkage. Here we report the bioisosteric replacement of the Ester Linkage with a thiazole moiety, yielding sulfonylnitrophenylthiazoles (SNPTs). An array of SNPTs representing optimal side chains from the MSNB series was constructed using parallel chemistry and evaluated to test their antagonism of the TR-coactivator interaction. Selected active compounds were evaluated in secondary confirmatory assays including regulation of thyroid response element driven transcription in reporter constructs and native genes. In addition the selected SNPTs were shown to be selective for TR relative to...
Jong Yeon Hwang - One of the best experts on this subject based on the ideXlab platform.
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synthesis and evaluation of methylsulfonylnitrobenzamides msnbas as inhibitors of the thyroid hormone receptor coactivator interaction
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Jong Yeon Hwang, Ramy R Attia, Angela K Carrillo, Michele C ConnellyAbstract: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.
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synthesis and evaluation of sulfonylnitrophenylthiazoles snpts as thyroid hormone receptor coactivator interaction inhibitors
Journal of Medicinal Chemistry, 2012Co-Authors: Jong Yeon Hwang, Ramy R Attia, Lei Yang, Andrew S Lemoff, Cynthia Jeffries, Michele C ConnellyAbstract:We previously identified a series of methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its coactivators. MSNBs inhibit coactivator binding through irreversible modification of cysteine 298 of the thyroid hormone receptor (TR). Although MSNBs have better pharmacological features than our first generation inhibitors (β-aminoketones), they contain a potentially unstable Ester Linkage. Here we report the bioisosteric replacement of the Ester Linkage with a thiazole moiety, yielding sulfonylnitrophenylthiazoles (SNPTs). An array of SNPTs representing optimal side chains from the MSNB series was constructed using parallel chemistry and evaluated to test their antagonism of the TR-coactivator interaction. Selected active compounds were evaluated in secondary confirmatory assays including regulation of thyroid response element driven transcription in reporter constructs and native genes. In addition the selected SNPTs were shown to be selective for TR relative to...
Ramy R Attia - One of the best experts on this subject based on the ideXlab platform.
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synthesis and evaluation of methylsulfonylnitrobenzamides msnbas as inhibitors of the thyroid hormone receptor coactivator interaction
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Jong Yeon Hwang, Ramy R Attia, Angela K Carrillo, Michele C ConnellyAbstract: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.
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synthesis and evaluation of sulfonylnitrophenylthiazoles snpts as thyroid hormone receptor coactivator interaction inhibitors
Journal of Medicinal Chemistry, 2012Co-Authors: Jong Yeon Hwang, Ramy R Attia, Lei Yang, Andrew S Lemoff, Cynthia Jeffries, Michele C ConnellyAbstract:We previously identified a series of methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its coactivators. MSNBs inhibit coactivator binding through irreversible modification of cysteine 298 of the thyroid hormone receptor (TR). Although MSNBs have better pharmacological features than our first generation inhibitors (β-aminoketones), they contain a potentially unstable Ester Linkage. Here we report the bioisosteric replacement of the Ester Linkage with a thiazole moiety, yielding sulfonylnitrophenylthiazoles (SNPTs). An array of SNPTs representing optimal side chains from the MSNB series was constructed using parallel chemistry and evaluated to test their antagonism of the TR-coactivator interaction. Selected active compounds were evaluated in secondary confirmatory assays including regulation of thyroid response element driven transcription in reporter constructs and native genes. In addition the selected SNPTs were shown to be selective for TR relative to...
Lidia Feliu - One of the best experts on this subject based on the ideXlab platform.
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Solid-Phase Synthesis of Cyclic Depsipeptides Containing a Tyrosine Phenyl Ester Bond
Organic Letters, 2016Co-Authors: Cristina Rosés, Cristina Camó, Kristy Vogels, Marta Planas, Lidia FeliuAbstract:The first solid-phase strategy for the synthesis of cyclic depsipeptides containing a phenyl Ester Linkage in their structure is described. The key steps of the synthesis were the formation of the phenyl Ester bond and the on-resin head-to-side-chain cyclization. The amino acid configuration significantly influenced the formation and the stability of the cyclic depsipeptides. The presence of a l-Tyr1 and a d-Tyr7 led to the most stable sequences.
Ronald Micura - One of the best experts on this subject based on the ideXlab platform.
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Functionalized polystyrene supports for solid-phase synthesis of glycyl-, alanyl-, and isoleucyl-RNA conjugates as hydrolysis-resistant mimics of peptidyl-tRNAs
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Jessica Steger, Ronald MicuraAbstract:RNA-peptide conjugates that mimic amino acid-charged tRNAs and peptidyl-tRNAs are of high importance for structural and functional investigations of ribosomal complexes. Here, we present the synthesis of glycyl-, alanyl-, and isoleucyladenosine modified solid supports that are eligible for the synthesis of stable 3′-aminoacyl- and 3′-peptidyl-tRNA termini with an amide instead of the natural Ester Linkage. The present work significantly expands the range of accessible peptidyl-tRNA mimics for ribosomal studies.