Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy.
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.
Velcicky
Juraj
J
Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. juraj.velcicky@novartis.com
Feifel
Roland
R
Hawtin
Stuart
S
Heng
Richard
R
Huppertz
Christine
C
Koch
Guido
G
Kroemer
Markus
M
Moebitz
Henrik
H
Revesz
Laszlo
L
Scheufler
Clemens
C
Schlapbach
Achim
A
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000099190:MAP-Kinase-Activated Kinase 2
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D000099190:MAP-Kinase-Activated Kinase 2; C436945:3-aminopyrazole