Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy

J Med Chem. 2007 Nov 29;50(24):5875-7. doi: 10.1021/jm700983a. Epub 2007 Nov 2.

Abstract

2D 1H-15N HMBC NMR acquired at natural abundance and DMSO titration monitored by 1D 1H NMR verified the existence of an intramolecular hydrogen bond that was designed to mimic the pyrimidinone ring of a class of kinase inhibitors. A scalar coupling across the hydrogen bond was detected in organic and aqueous solvent, suggesting a simple and general approach for testing the propensity of intramolecular hydrogen bonds to stabilize pseudo-rings in drug scaffolds.

MeSH terms

  • Dimethyl Sulfoxide
  • Drug Design*
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Pyridines / chemistry*
  • Pyridones / chemistry*
  • Pyrimidines / chemistry*
  • Solubility
  • Water

Substances

  • PD 166326
  • Pyridines
  • Pyridones
  • Pyrimidines
  • Water
  • PD 180970
  • Dimethyl Sulfoxide