Studies on the 4-benzoylpyridine-3-carboxamide entity as a fragment model of the Isoniazid-NAD adduct.
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.
Broussy
Sylvain
S
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse cedex 4, France.
Bernardes-Génisson
Vania
V
Gornitzka
Heinz
H
Bernadou
Jean
J
Meunier
Bernard
B
D018360:Crystallography, X-Ray; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D009243:NAD / Q000031:analogs & derivatives / Q000737:chemistry*; D009525:Niacin / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D014376:Tuberculosis / Q000188:drug therapy
D011725:Pyridines; D009243:NAD; D009525:Niacin; C066738:4-benzoylpyridine; D007538:Isoniazid