| Autor: |
Huang L; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. r.manetsch@northeastern.edu., Parvatkar PT; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. r.manetsch@northeastern.edu., Wagner A; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. r.manetsch@northeastern.edu., Kulkarni SS; Department of Chemistry, University of South Florida, Tampa, FL 33620, USA., Manetsch R; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. r.manetsch@northeastern.edu.; Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.; Center for Drug Discovery, Northeastern University, Boston, MA 02115, USA.; Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA 02115, USA. |
| Abstrakt: |
Capitalizing on our previous kinetic target-guided synthesis (KTGS) involving the sulfo-click reaction to form N -acylsulfonamide-linked inhibitors in the presence of the protein-protein interaction target Mcl-1, we herein report a seleno-click approach for amide-linked inhibitors of Mcl-1. The seleno-click reaction leverages the enhanced reactivity of selenocarboxylates, enabling the templated amidation with electron-rich azides, thereby expanding the scope of KTGS. The potential of this approach is demonstrated by generating N -benzyl-5-(4-isopropylthiophenol)-2-hydroxyl nicotinamide, a known Mcl-1 inhibitor featuring an amide, via KTGS at 37 °C against Mcl-1. Notably, the seleno-click strategy was also effective at 4 °C, offering a variant for thermally sensitive biological targets. |
