- Regioselective one-pot C-N coupling of substituted naphthoquinones: Selective intramolecular ring fusion of sulfonamides
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The first one-pot copper-catalyzed highly regioselective C-N bond formation between aryl/alkyl amines and sulfonamide-substituted naphthoquinones was accomplished. Facile chemoselective routes obtained diverse ring-opening 6-amino/anilino-naphthalen-dione-1-sulfonamides and ring-fused 6-amino/aniline-5H-naphth[1,8-cd]isothiazol-5-one,1,1-dioxides with great functional group tolerance. Regiochemistry was confirmed by 1D- and 2D-NMRs.
- Yu, Wenying,Li, Chenglong
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- STAT3 INHIBITORS AND THEIR ANTICANCER USE
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In one aspect, the invention relates to substituted substituted 6-amino-5,8-dioxo-5,8- dihydronaphthalene- 1 -sulfonamide analogs and derivatives thereof, substituted 4-amino-5H- naphtho[l,8-cd]isothiazol-5-one 1,1-dioxide analogs and derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00473; 00476; 00477
(2014/03/22)
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- Discovery of novel STAT3 small molecule inhibitors via in silico site-directed fragment-based drug design
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Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been validated as an attractive therapeutic target for cancer therapy. To stop both STAT3 activation and dimerization, a viable strategy is to design inhibitors blocking its SH2 domain phosphotyrosine binding site that is responsible for both actions. A new fragment-based drug design (FBDD) strategy, in silico site-directed FBDD, was applied in this study. A designed novel compound, 5,8-dioxo-6-(pyridin-3-ylamino)-5,8-dihydronaphthalene-1-sulfonamide (LY5), was confirmed to bind to STAT3 SH2 by fluorescence polarization assay. In addition, four out of the five chosen compounds have IC50 values lower than 5 μM for the U2OS cancer cells. 8 (LY5) has an IC50 range in 0.5-1.4 μM in various cancer cell lines. 8 also suppresses tumor growth in an in vivo mouse model. This study has demonstrated the utility of this approach and could be used to other drug targets in general.
- Yu, Wenying,Xiao, Hui,Lin, Jiayuh,Li, Chenglong
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p. 4402 - 4412
(2013/07/19)
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