Abstract
Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.
MeSH terms
-
Azabicyclo Compounds / chemical synthesis
-
Azabicyclo Compounds / chemistry*
-
Celecoxib / chemical synthesis*
-
Celecoxib / chemistry
-
Click Chemistry
-
Cycloaddition Reaction
-
Cyclooxygenase 2 / chemistry
-
Cyclooxygenase Inhibitors / chemical synthesis
-
Cyclooxygenase Inhibitors / chemistry
-
Doxorubicin / chemical synthesis*
-
Enzyme Assays
-
Heterocyclic Compounds, 3-Ring / chemical synthesis
-
Heterocyclic Compounds, 3-Ring / chemistry*
-
Humans
-
Models, Chemical
-
Prodrugs / chemical synthesis
-
Prodrugs / chemistry*
-
Quantum Theory
-
Sydnones / chemical synthesis
-
Sydnones / chemistry*
Substances
-
Azabicyclo Compounds
-
Cyclooxygenase Inhibitors
-
Heterocyclic Compounds, 3-Ring
-
Prodrugs
-
Sydnones
-
Doxorubicin
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
Celecoxib