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.
authors: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors: Jong Yeon
authors: JY
authors: Hwang
authors: Ramy R
authors: RR
authors: Attia
authors: Angela K
authors: AK
authors: Carrillo
authors: Michele C
authors: MC
authors: Connelly
authors: R Kiplin
authors: RK
authors: Guy
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D056920:Nuclear Receptor Coactivator 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D014162:Transfection
chemical_list: D001549:Benzamides; D011988:Receptors, Thyroid Hormone; D013844:Thiazoles; D056920:Nuclear Receptor Coactivator 1