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Literature DB >> 20231096

Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors.

Carole Pissot-Soldermann¹, Marc Gerspacher, Pascal Furet, Christoph Gaul, Philipp Holzer, Clive McCarthy, Thomas Radimerski, Catherine H Regnier, Fabienne Baffert, Peter Drueckes, Gisele A Tavares, Eric Vangrevelinghe, Francesca Blasco, Giorgio Ottaviani, Flavio Ossola, Julien Scesa, Janitha Reetz.

Abstract

We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation. Copyright 2010 Elsevier Ltd. All rights reserved.

Entities: Chemical Gene Species

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Year: 2010 PMID： 20231096 DOI： 10.1016/j.bmcl.2010.02.056

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

8 in total

1. Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent.

Authors: Rita Andraos; Zhiyan Qian; Débora Bonenfant; Joëlle Rubert; Eric Vangrevelinghe; Clemens Scheufler; Fanny Marque; Catherine H Régnier; Alain De Pover; Hugues Ryckelynck; Neha Bhagwat; Priya Koppikar; Aviva Goel; Lorenza Wyder; Gisele Tavares; Fabienne Baffert; Carole Pissot-Soldermann; Paul W Manley; Christoph Gaul; Hans Voshol; Ross L Levine; William R Sellers; Francesco Hofmann; Thomas Radimerski
Journal: Cancer Discov Date: 2012-05-03 Impact factor: 39.397

2. Molecular dynamics and integrated pharmacophore-based identification of dual [Formula: see text] inhibitors.

Authors: Maninder Kaur; Pankaj Kumar Singh; Manjinder Singh; Renu Bahadur; Om Silakari
Journal: Mol Divers Date: 2017-11-14 Impact factor: 2.943

3. Dual inhibitors of Janus kinase 2 and 3 (JAK2/3): designing by pharmacophore- and docking-based virtual screening approach.

Authors: Haneesh Jasuja; Navriti Chadha; Maninder Kaur; Om Silakari
Journal: Mol Divers Date: 2014-01-11 Impact factor: 2.943

Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors.

1. Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent.

2. Molecular dynamics and integrated pharmacophore-based identification of dual [Formula: see text] inhibitors.

3. Dual inhibitors of Janus kinase 2 and 3 (JAK2/3): designing by pharmacophore- and docking-based virtual screening approach.

Review 4. The use of structural biology in Janus kinase targeted drug discovery.

5. Understanding the structural features of JAK2 inhibitors: a combined 3D-QSAR, DFT and molecular dynamics study.

6. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival.

7. Identification of Potent and Selective JAK1 Lead Compounds Through Ligand-Based Drug Design Approaches.

8. Discovery of JAK2/3 Inhibitors from Quinoxalinone-Containing Compounds.