2-Thiophenecarboxamide, N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methyl-

Description

MARK-IN-2 is a potent microtubule affinity regulating kinase (MARK) inhibitor with an IC50 of 5 nM.

MARK-IN-2 (Compound 27) is a potent MARK inhibitor. Inhibition of MARK represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer's disease. MARK-IN-2 inhibits MARK3 with an IC50 of 5 nM. MARK-IN-2 also inhibits MARK3 in primary cell culture of rat cortical neurons with an IC50 of 280 nM[1].

Characterization of the i.v. pharmacokinetic properties of MARK-IN-2 in rat and dog reveals reasonable volumes of distribution but moderate to high clearance and short half-lives. MARK-IN-2 (Compound 27) has moderate terminal elimination half-life (t1/2=0.7 h, and 1 h for rat and dog) [1].

References

[1]. Sloman DL, et al. Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4362-6.