药物样分子弹簧：硫(VI)双环丁烷弹头

Sulfur(VI) bicyclobutane is highly strained because of two three-membered hydrocarbon rings that share a common bond. The C–C bridge breaks upon nucleophilic attack by the cysteine side chain, leading to covalent modification of the targeted cysteine residue in the protein. A readily accessible reagent with a less electron-deficient oxidation state (+IV) of sulfur allows formation of S–N bonds in the presence of various functional groups. rated into covalent kinase inhibitors, the bicy- clobutane warheads yielded compounds with bioactivity comparable to that of the acryl- amide parent molecules, but with markedly im- proved selectivity when assessed for off-target activity and through proteomic analyses of re- activity across the proteins expressed in target cells. …