157252-24-9Relevant articles and documents
Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein Interaction
Chen, Jinshui,Song, Yun,Bojadzic, Damir,Tamayo-Garcia, Alejandro,Landin, Ana Marie,Blomberg, Bonnie B.,Buchwald, Peter
, p. 8906 - 8922 (2017)
Costimulatory interactions are required for T cell activation and development of an effective immune response; hence, they are valuable therapeutic targets for immunomodulation. However, they, as all other protein-protein interactions, are difficult to target by small molecules. Here, we report the identification of novel small-molecule inhibitors of the CD40-CD40L interaction designed starting from the chemical space of organic dyes. For the most promising compounds such as DRI-C21045, activity (IC50) in the low micromolar range has been confirmed in cell assays including inhibition of CD40L-induced activation in NF-κB sensor cells, THP-1 myeloid cells, and primary human B cells as well as in murine allogeneic skin transplant and alloantigen-induced T cell expansion in draining lymph node experiments. Specificity versus other TNF-superfamily interactions (TNF-R1-TNF-α) and lack of cytotoxicity have also been confirmed at these concentrations. These novel compounds provide proof-of-principle evidence for the possibility of small-molecule inhibition of costimulatory protein-protein interactions, establish the structural requirements needed for efficient CD40-CD40L inhibition, and serve to guide the search for such immune therapeutics.
Intermolecular photoaddition reaction of arenecarbothioamides to 2- methoxy- and 2-trimethylsiloxyfurans. Facile synthesis of arene-fused aminobenzoates by novel photoinduced benzannulation
Oda, Kazuaki,Sakai, Masayuki,Machida, Minoru
, p. 584 - 589 (1997)
Irradiation of arenecarbothioamides with 2-methoxyfuran in benzene solution gave arene-fused aminobenzoates in moderate yields accompanied by small amounts of arylpyrroles or arylthiophenes. In the case of 2- trimethylsiloxyfuran, arenecarbothioamides gave arene-fused aminobenzoates in good yields as sole products. It was demonstrated that certain furan derivatives are potentially useful as building blocks in photoinduced benzannulation.
Bicyclic modulators of androgen receptor function
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, (2008/06/13)
The invention provides compounds of the formula I wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia, and also provided are pharmaceutical compositions containing such compounds.
