Shultz, Michael D. published the artcileOptimization of the in vitro cardiac safety of hydroxamate-based Histone deacetylase inhibitors, Quality Control of 5654-92-2, the main research area is hydroxamate derivative preparation SAR HDAC inhibotor anticancer.
Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homol. between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homol. model, two compounds, I and II, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.
Journal of Medicinal Chemistry published new progress about Aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Quality Control of 5654-92-2.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles