s Approaches to a Multitargeting Drug Development: First Profiled 3- Ethoxycarbonyl-1-aza-9-oxafluorenes Representing a Perspective Compound Class Targeting Alzheimer Disease Relevant Kinases CDK1, CDK5 and GSK-3β

Since Alzheimer disease (AD) is a multifactorial disease, recent therapeutical approaches concentrate on the development of a multitargeting drug. Various protein kinases are known to be involved in the progression of AD. A first series of 3-ethoxycarbonyl-1-aza-9-oxafluorenes has been synthesized and biologically evaluated as AD-relevant protein kinase inhibitors. A concentration-dependent inhibition of important AD-relevant kinases has been characterized after the selectivity of kinase inhibition had been demonstrated. Structure-activity relationships of protein kinase inhibition are discussed and first multitargeting inhibitors have been identified.