Substituted (e)-n'-(1-phenylethylidene) benzohydrazide analogs as histone demethylase inhiitors

Abstract

In one aspect, the invention relates to substituted (E)-N'-(1- phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Description

Background technique [0001] Over the past few decades, it has become clear that epigenetic variations (which alter gene activity without altering DNA sequence) and genetic errors contribute to the development and progression of cancer (Tsai, H.C. and Baylin, S.B. Cell Res 2011, 21 (3), 502-17; and Fullgrabe, J., Kavanagh, E., and Joseph, B. Oncogene 2011). The regulation of modifications on DNA and DNA-bound proteins has been an area of ​​intense interest, and the enzymes involved in these processes have been suggested as a new class of protein targets for drug development. The main proteins that bind to DNA are histones. Histone tails undergo a variety of post-translational modifications, such as phosphorylation, acetylation, methylation, and ubiquitination, and these modifications, especially acetylation and methylation on lysine residues, are involved in the regulation of gene expression Plays a major role and is often dysregulated in cancer (Fullgrabe, J., Kavanagh, E., ...

AI Technical Summary

Problems solved by technology

Although advances in drug discovery have focused on identifying inhibitors of LSD1 and / or LSD2 protein activity, potent, potent and selective LSD1 or LSD2 inhibitors are still lacking

Furthermore, there is a lack of compounds effective in the treatment of cancer and other diseases associated with dysfunctional LSD1 and / or LSD2

Images