Aza-analogue dibenzepinone scaffolds as p38 mitogen-activated protein kinase inhibitors: design, synthesis, and biological data of inhibitors with improved physicochemical properties.
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.
Karcher
Solveigh C
SC
Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-Universität, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
Laufer
Stefan A
SA
D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D001372:Aza Compounds; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases