Design, synthesis and biological evaluation of hypolipidemic compounds based on BRD4 inhibitor RVX-208

Bioorg Med Chem Lett. 2019 Aug 15;29(16):2168-2172. doi: 10.1016/j.bmcl.2019.06.028. Epub 2019 Jun 20.

Abstract

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.

Keywords: BRD4 inhibitor; Dual-active; Hyperlipoidemia; Phenoxyacetic derivatives; RVX-208.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / antagonists & inhibitors*
  • Humans
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • Hypolipidemic Agents
  • Transcription Factors