In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part I

Autor:	Laszlo Revesz, Achim Schlapbach, Reiner Aichholz, Roland Feifel, Stuart Hawtin, Richard Heng, Peter Hiestand, Wolfgang Jahnke, Guido Koch, Markus Kroemer, Henrik Möbitz, Clemens Scheufler, Juraj Velcicky, Christine Huppertz
Rok vydání:	2010
Předmět:	MAPK/ERK pathway Lactams Clinical Biochemistry Administration Oral Pharmaceutical Science Protein Serine-Threonine Kinases Crystallography X-Ray Heterocyclic Compounds 4 or More Rings Biochemistry Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery Animals Humans Structure–activity relationship Pyrroles Amino Acids Isoquinoline Protein Kinase Inhibitors Molecular Biology Binding Sites biology Tumor Necrosis Factor-alpha Chemistry Kinase Organic Chemistry Intracellular Signaling Peptides and Proteins Ketones Isoquinolines In vitro Enzyme inhibitor Mitogen-activated protein kinase biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:4715-4718
ISSN:	0960-894X
Popis:	Pyrrolo[2,3-f]isoquinoline based amino acids, tetracyclic lactams and cyclic ketone analogues are described as novel MK2 inhibitors with IC(50) as low as 5nM and good selectivity profiles against a number of related kinases including ERK, p38alpha and JNKs. TNFalpha release was suppressed from human peripheral blood mononuclear cells (hPBMCs), and a representative compound inhibited LPS induced TNFalpha release in mice illustrating the potential of this series to provide orally active MK2 inhibitors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0fac2d9fd29dbe422fca2ca8db35aa03 https://doi.org/10.1016/j.bmcl.2010.04.024 Zobrazit plný text záznamu Full Text from ScienceDirect