Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy

Juraj Velcicky; Roland Feifel; Stuart Hawtin; Richard Heng; Christine Huppertz; Guido Koch; Markus Kroemer; Henrik Moebitz; Laszlo Revesz; Clemens Scheufler; Achim Schlapbach

doi:10.1016/j.bmcl.2009.10.138

Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1293-7. doi: 10.1016/j.bmcl.2009.10.138. Epub 2009 Nov 3.

Authors

Juraj Velcicky¹, Roland Feifel, Stuart Hawtin, Richard Heng, Christine Huppertz, Guido Koch, Markus Kroemer, Henrik Moebitz, Laszlo Revesz, Clemens Scheufler, Achim Schlapbach

Affiliation

¹ Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. [email protected]

PMID: 20060294
DOI: 10.1016/j.bmcl.2009.10.138

Abstract

New, selective 3-aminopyrazole based MK2-inhibitors were discovered by scaffold hopping strategy. The new derivatives proved to inhibit intracellular phosphorylation of hsp27 as well as LPS-induced TNFalpha release in cells. In addition, selected derivative 14e also inhibited LPS-induced TNFalpha release in vivo.

Publication types

Comparative Study

MeSH terms

Cell Line, Tumor
Cells, Cultured
Crystallography, X-Ray
Drug Discovery* / methods
Humans
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
Intracellular Signaling Peptides and Proteins / metabolism
Protein Conformation
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / metabolism
Pyrazoles / chemistry*
Pyrazoles / metabolism
Pyrazoles / pharmacology

Substances

3-aminopyrazole
Intracellular Signaling Peptides and Proteins
Pyrazoles
MAP-kinase-activated kinase 2
Protein Serine-Threonine Kinases