Self-organizing molecular field analysis on human β-secretase nonpeptide inhibitors: 5, 5-disubstituted aminohydantoins

Eur J Med Chem. 2011 Jan;46(1):58-64. doi: 10.1016/j.ejmech.2010.10.014. Epub 2010 Nov 19.


5, 5-disubstituted aminohydantoins have been recently reported as potent and selective human β-secretase (BACE-1) inhibitors. Self-Organizing Molecular Field Analysis (SOMFA) is used to study the correlation between the molecular properties and biological activities of the 5, 5-disubstituted aminohydantoins inhibitors. Four different alignments and two charge-assigning methods were investigated. The model derived from the superposition of docked conformation with AM1 charge showed satisfied predictive ability, which has good non-cross-validated r(2) (0.842), cross-validated q(2) (0.792), F-test value (254.75) and satisfied predictive ability r(2)(pred) (0.721). Analysis of SOMFA model may provide some useful information in the design of BACE-1 inhibitors with better spectrum of activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / chemistry
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / chemistry
  • Aspartic Acid Endopeptidases / metabolism
  • Drug Design*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydantoins / chemistry*
  • Hydantoins / metabolism
  • Hydantoins / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Quantitative Structure-Activity Relationship


  • Enzyme Inhibitors
  • Hydantoins
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human