New evolutions in the BACE1 inhibitor field from 2014 to 2018

Bioorg Med Chem Lett. 2019 Mar 15;29(6):761-777. doi: 10.1016/j.bmcl.2018.12.049. Epub 2019 Jan 4.

Abstract

β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors offer the potential of disease-modifying treatment for Alzheimer's disease (AD). Since 2014, major breakthroughs have appeared in the field of BACE1 inhibitors. This review provides an overview of amidine-based BACE1 inhibitors between 2014 and 2018. Herein are summarized i) the structure-activity relationship, ii) the physiological results and iii) the potential risks from a lack of selectivity. This review also summarizes clinical scope, results and outlook of the compounds that have been or are currently under development in clinical trials.

Keywords: Alzheimer’s; Amidine; Amyloid; BACE; BACE1; Inhibitor; Neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amidines / chemistry
  • Amidines / therapeutic use*
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Animals
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / therapeutic use*
  • Humans
  • Molecular Structure
  • Protease Inhibitors / chemistry*
  • Structure-Activity Relationship

Substances

  • Amidines
  • Heterocyclic Compounds
  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases