These investigations suggested the ability of the selected compounds to pass the blood brain barrier (BBB) (aside from them compounds <b>2c</b> and <b>3c</b>) and affect tau proteins, which will be valuable for the treatment of Alzheimer's disease, particularly compound <b>5</b> which does not require any SAR modifications to attain the BBB.
Interlink between Pregnane X Receptor (PXR) and P-glycoprotein (Pgp) at the blood brain barrier (BBB) has raised hope toward a new disease modifying therapy in AD.
The kinase MARK2/Par-1 plays key roles in several cell processes, including neurodegeneration such as Alzheimer disease by phosphorylating tau and detaching it from microtubules.
Microtubule affinity regulating kinase (MARK) and PAR-1 have been identified as physiological tau kinases, and aberrant phosphorylation of MARK/PAR-1 target sites in tau has been observed in AD patients and animal models.