5 research outputs found
機能的三尖弁逆流症例における三尖弁輪の4次元解析
広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora
Concise SAR Exploration Based on the “Head-to-Tail” Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds
In typical kinase inhibitor programs,
a hinge binder showing best
potency with preferential specificity is initially selected, followed
by fine-tuning of the accompanying substituents on its core module.
A shortcoming of this approach is that the exclusive focus on a single
chemotype can endanger all the analogues in the series if a critical
shortcoming is revealed. Thus, an early evaluation of structure–activity
relationships (SARs) can mitigate unforeseen outcomes within a series
of multiple compounds, although there have been very few examples
to follow such a policy. PI4KIIIα is one of four mammalian phosphatidylinositol-4
kinases and has recently drawn significant attention as an emerging
target for hepatitis C virus (HCV) treatment. In this letter, a novel
“head-to-tail” approach to discover a diverse set of
PI4KIIIα inhibitors is reported. We believe this method will
generate distinct core scaffolds, a rational strategy to circumvent
potential risks in general kinase programs