396090-99-6Relevant academic research and scientific papers
Discovery of potent and bioavailable GSK-3β inhibitors
Gong, Leyi,Hirschfeld, Don,Tan, Yun-Chou,Heather Hogg,Peltz, Gary,Avnur, Zafrira,Dunten, Pete
scheme or table, p. 1693 - 1696 (2010/07/05)
Here we report on the discovery of a series of maleimides which have high potency and good selectivity for GSK-3β. The incorporation of polar groups afforded compounds with good bioavailability. The most potent compound 34 has an IC50 of 0.6 nM for GSK-3β, over 100-fold selectivity against a panel of other kinases, and shows efficacy in rat osteoporosis models. The X-ray structure of GSK-3β protein with 34 bound revealed the binding mode of the template and provided insights for future optimization opportunities.
Inhibitors of Protein Kinase C. 1. 2,3-Bisarylmaleimides
Davis, Peter D.,Hill, Christopher H.,Lawton, Geoffrey,Nixon, John S.,Wilkinson, Sandra E.,et al.
, p. 177 - 184 (2007/10/02)
The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described.These 2,3-bisarylmaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a.Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11 μM).In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67 μM).Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).
