Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study?

RSC Advances Pub Date: 2017-01-17 DOI: 10.1039/C6RA24953A

Abstract

Protein kinase B (PknB) is an essential serine/threonine protein kinase required for Mycobacterium tuberculosis (M. tb) cell division and cell-wall biosynthesis. A high throughput screen using PknB identified a (E)-4-oxo-crotonic acid inhibitor, named YH-8, which was used as a scaffold for SAR investigations. A significant improvement in enzyme affinity was achieved. The results indicated that the α,β-unsaturated ketone scaffold and “trans-” configuration are essential for the activity against PknB. And compounds with an aryl group, especially with electron-withdrawing substituents on benzene ring, exhibited four fold potency than that of YH-8.

Graphical abstract: Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study
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