55478-08-5Relevant articles and documents
Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-XLand BCL-2
Roy, Michael J.,Vom, Amelia,Okamoto, Toru,Smith, Brian J.,Birkinshaw, Richard W.,Yang, Hong,Abdo, Houda,White, Christine. A.,Segal, David,Huang, David C. S.,Baell, Jonathan B.,Colman, Peter M.,Czabotar, Peter E.,Lessene, Guillaume
, p. 5447 - 5469 (2021/05/31)
The BCL-2 family of proteins (including the prosurvival proteins BCL-2, BCL-XL, and MCL-1) is an important target for the development of novel anticancer therapeutics. Despite the challenges of targeting protein-protein interaction (PPI) interfaces with small molecules, a number of inhibitors (called BH3 mimetics) have entered the clinic and the BCL-2 inhibitor, ABT-199/venetoclax, is already proving transformative. For BCL-XL, new validated chemical series are desirable. Here, we outline the crystallography-guided development of a structurally distinct series of BCL-XL/BCL-2 inhibitors based on a benzoylurea scaffold, originally proposed as α-helix mimetics. We describe structure-guided exploration of a cryptic "p5"pocket identified in BCL-XL. This work yields novel inhibitors with submicromolar binding, with marked selectivity toward BCL-XL. Extension into the hydrophobic p2 pocket yielded the most potent inhibitor in the series, binding strongly to BCL-XL and BCL-2 (nanomolar-range half-maximal inhibitory concentration (IC50)) and displaying mechanism-based killing in cells engineered to depend on BCL-XL for survival.
Synthesis and photophysics of benzazole based triazoles with amino acid-derived pendant units. Multiparametric optical sensors for BSA and CT-DNA in solution
Debia, Natalí P.,Rodríguez, Juan J.P.,da Silveira, Carolina H.,Chaves, Otavio A.,Iglesias, Bernardo A.,Rodembusch, Fabiano S.,Lüdtke, Diogo S.
, (2020/04/27)
Herein we report the synthesis of a series of amino acid-derived triazoles by an organocatalytic cycloaddition reaction between azides and carbonyl compounds, catalyzed by a simple amine. These compounds present absorption maxima located in the UV-B ascribed to fully spin and symmetry allowed electronic transitions and a main fluorescence emission in the UV-A (~380 nm) with a relatively large Stokes shift (5700 cm?1). No significant solvatochromism was observed in both ground and excited states. Unexpectedly, the benzoxazole derivatives presented much higher fluorescence quantum yield values (40–80%) of compared to the sulfur analogues (3–6%). In addition, the DNA binding assays indicated that these compounds presented strong interaction with CT-DNA, which could be attributed to π-stacking and intermolecular hydrogen-bonding. The interaction of the benzazoles with bovine serum albumin (BSA) was also investigated, where a suppression mechanism was observed. In each case, docking was performed to better understand the observed interactions.
Synthesis of thioesters by simultaneous activation of carboxylic acids and alcohols using PPh3/NBS with benzyltriethylammonium tetrathiomolybdate as the sulfur transfer reagent
Gopinath, Purushothaman,Vidyarini, Ravindran Sasitha,Chandrasekaran, Srinivasan
experimental part, p. 6043 - 6047 (2010/03/25)
A new and simple route for the synthesis of thioesters starting from carboxylic acids and alcohols is reported by using tetrathiomolybdate as the key sulfur transfer reagent, Triphenylphosphane and N-bromosuccinimide were used for the activation of the ca
