Synthesis, Hydrolysis, and Analgesic Activity of 3-[3-(1-arylethylcarbamoyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-1-yl]propanenitriles and Their Derivatives

Abstract

X-ray diffraction analysis studies showed that in a mixture of HCl, AcOH, and H₂O, hydrolysis of several 3-[3-(1-arylethylcarbamoyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-1-yl]propanenitriles proceeded by an anomalous pathway to yield 4-hydroxy-1-(2-carboxyethyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid. These experiments showed that methylation of the methylene bridge separating the amide nitrogen atom and the aromatic nucleus led to a drop in activity. At the same time, hydration of quinolinylpropanenitriles to the corresponding propanamides was seen as a successful approach to chemical modification enhancing analgesic properties.