Novel Azaborine-Based Inhibitors of Histone Deacetylases (HDACs)
Martin Behringer, Markus Schweipert, Enna E. Peters, Aleksandra Kopranovic, Franz-Josef Meyer-Almes
TL;DR
This paper introduces new HDAC inhibitors using azaborine rings, which improve water solubility and offer a way to bypass existing patents.
Contribution
The study presents novel azaborine-based HDAC inhibitors with enhanced solubility and activity.
Findings
Nearly half of the tested molecules showed inhibitory activity against HDAC1, HDAC4, or HDAC8.
Three compounds had nanomolar IC50 values, indicating strong inhibitory potential.
Azaborine rings can be effectively used as building blocks in HDAC inhibitors.
Abstract
Aromatic ring systems appear ubiquitously in active pharmaceutical substances, such as FDA-approved histone deacetylase inhibitors. However, these rings reduce the water solubility of the molecules, which is a disadvantage during application. To address this problem, azaborine rings may be substituted for conventional aromatic ring systems. These are obtained by replacing two adjacent carbon atoms with boron and nitrogen. Incorporating B–N analogs in place of aromatic rings not only enhances structural diversity but also provides a strategy to navigate around patent-protected scaffolds. We synthesized azaborines, which are isosteric to naphthalene and indole, and utilized them as capping units for HDAC inhibitors. These molecules were attached to various aliphatic and aromatic linkers with different zinc-binding units, used in established active compounds. Nearly half of the twenty-four…
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Taxonomy
TopicsHistone Deacetylase Inhibitors Research · Synthetic Organic Chemistry Methods · Peptidase Inhibition and Analysis