Studies on the 4-benzoylpyridine-3-carboxamide entity as a fragment model of the Isoniazid-NAD adduct

Org Biomol Chem. 2005 Feb 21;3(4):666-9. doi: 10.1039/b415439h. Epub 2005 Jan 13.

Abstract

An ortho-metallation-electrophilic substitution sequence was employed as a key step to build the 4-benzoylpyridine framework. It was found that 4-benzoylpyridine-3-carboxamide and an N-pyridyl alkylated derivative both exist in a unique cyclized hemiamidal structure, not in the usually expected keto-amide open form. These structures represent fragment models of the Isoniazid-NAD adducts involved in the mechanism of action of the antituberculous drug Isoniazid.

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Isoniazid / analogs & derivatives
  • Isoniazid / chemistry*
  • Molecular Conformation
  • Molecular Structure
  • NAD / analogs & derivatives
  • NAD / chemistry*
  • Niacin / chemistry
  • Pyridines / chemistry
  • Tuberculosis / drug therapy

Substances

  • Pyridines
  • NAD
  • Niacin
  • 4-benzoylpyridine
  • Isoniazid