Aims: Design of sulfonamide-triazine derivatives as JAK1 inhibitors.
Background: JAK1 is a kinase involved in different autoimmune diseases. JAK1 inhibitors have shown promising results
in treating autoimmune diseases.
Objectives: To design new JAK1 inhibitors based on sulfonamides-triazine conjugates capable of binding interactions
comparable to observed interactions anchoring potent crystallographic JAK1 inhibitors.
Methods: The crystallographic structures of 4 diverse nanomolar inhibitors complexed within JAK1 were used to guide
the synthesis of new diaminotriazine-sulfonamide-based JAK1 inhibitors.
Results: Nineteen compounds have been prepared some of which exhibited low micromolar IC50 values against JAK1.
Conclusions: Crystallographic complexes of diverse JAK1 inhibitors were successfully used to guide the synthesis of
novel sulfonamide-triazine-based low micromolar JAK1 inhibitors.