Molecular and crystal structures of 2-(2-pyridyl)thioacetamide derivatives and possible relationship with inhibitory activity for gastric acid secretion.
As a possible method to determine the key atoms and their spatial orientation which are necessary for the gastric mucosal protective and antisecretory activity, crystal structures of sixteen 2-(2-pyridyl) thioacetamide derivatives have been analyzed by the X-ray diffraction method. The characteristics of the molecular and crystal structures of the derivatives are described in this paper. The energetic stability of the molecular conformation is also investigated by means of the molecular force field method. Using the conformational data, a possible relationship between the stereostructure and inhibitory activity for gastric acid secretion is considered by QSAR analyses. The results suggest that the activity is related to the overall molecular conformation, and that the spatial distribution of the side-chain polar atoms with respect to the fixed pyridine is especially important for the activity.
Ohishi
H
H
Osaka University of Pharmaceutical Sciences, Japan.
Fujimori
Y
Y
In
Y
Y
Ishida
T
T
Inoue
M
M
Sato
F
F
Okitsu
M
M
Ohno
T
T
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D013853:Thioacetamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014961:X-Ray Diffraction
D013853:Thioacetamide