Design and Synthesis of New JAK1 Inhibitors based on SulfonamideTriazine Conjugates

(E-pub Ahead of Print)

Author(s): Safa Daoud, Mutasem O. Taha*

Journal Name: Current Computer-Aided Drug Design


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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

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1573409916666201224152253

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