Aza-analogue dibenzepinone scaffolds as p38 mitogen-activated protein kinase inhibitors: design, synthesis, and biological data of inhibitors with improved physicochemical properties

Solveigh C Karcher; Stefan A Laufer

doi:10.1021/jm801291f

Aza-analogue dibenzepinone scaffolds as p38 mitogen-activated protein kinase inhibitors: design, synthesis, and biological data of inhibitors with improved physicochemical properties

J Med Chem. 2009 Mar 26;52(6):1778-82. doi: 10.1021/jm801291f.

Authors

Solveigh C Karcher¹, Stefan A Laufer

Affiliation

¹ Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 8, 72076 Tübingen, Germany.

PMID: 19253982
DOI: 10.1021/jm801291f

Abstract

We recently described a promising novel class of p38 mitogen activated protein (MAP()) kinase inhibitors with dibenzepinone-scaffolds. To optimize their physicochemical properties, characterized by calculated log P values and measured lipophilicity (chromatographic hydrophobicity index = CHI), we synthesized aza-analogue dibenzepinones. Here, we present the synthesis and biological data of compounds with the novel aza-dibenzepinone scaffolds. Although these aza-analogues revealed an improved aqueous solubility, introduction of nitrogen was not effective in the p38 MAPK enzyme assay.

MeSH terms

Aza Compounds / chemistry
Aza Compounds / pharmacology*
Drug Design*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

Aza Compounds
Protein Kinase Inhibitors
p38 Mitogen-Activated Protein Kinases