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Design and Synthesis of New JAK1 Inhibitors based on SulfonamideTriazine Conjugates

Author(s):

Safa Daoud and Mutasem O. Taha*   Pages 1 - 11 ( 11 )

Abstract:


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.

Keywords:

JAK1 inhibitors, sulfonamides, diamino-triazines, docking, dose-response, crystallographic complexes

Affiliation:

Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science Private University, Amman, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science Private University, Amman



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