| Structural highlights
Publication Abstract from PubMed
Inhibition of microtubule affinity regulating kinase (MARK) represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer's disease. This manuscript outlines efforts to optimize a pyrazolopyrimidine series of MARK inhibitors by focusing on improvements in potency, physical properties and attributes amenable to CNS penetration. A unique cylcyclohexyldiamine scaffold was identified that led to remarkable improvements in potency, opening up opportunities to reduce MW, Pgp efflux and improve pharmacokinetic properties while also conferring improved solubility.
Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties.,Sloman DL, Noucti N, Altman MD, Chen D, Mislak AC, Szewczak A, Hayashi M, Warren L, Dellovade T, Wu Z, Marcus J, Walker D, Su HP, Edavettal SC, Munshi S, Hutton M, Nuthall H, Stanton MG Bioorg Med Chem Lett. 2016 Sep 1;26(17):4362-6. doi: 10.1016/j.bmcl.2016.02.003. , Epub 2016 Feb 6. PMID:27491711[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sloman DL, Noucti N, Altman MD, Chen D, Mislak AC, Szewczak A, Hayashi M, Warren L, Dellovade T, Wu Z, Marcus J, Walker D, Su HP, Edavettal SC, Munshi S, Hutton M, Nuthall H, Stanton MG. Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4362-6. doi: 10.1016/j.bmcl.2016.02.003. , Epub 2016 Feb 6. PMID:27491711 doi:http://dx.doi.org/10.1016/j.bmcl.2016.02.003
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