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Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

General Research Article

Design and Synthesis of New JAK1 Inhibitors based on Sulfonamide- Triazine Conjugates

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

Volume 17, Issue 7, 2021

Published on: 24 December, 2020

Page: [916 - 926] Pages: 11

DOI: 10.2174/1573409916666201224152253

Price: $65

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.

Graphical Abstract


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