O. M. Glozman, L. A. Zhmurenko, V. P. Lezina
Nov 1, 2001
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Journal
Pharmaceutical Chemistry Journal
Abstract
The class of 2and 4-aminopyridinecarboxylic acid derivatives contains compounds possessing anxiolytic, anticonvulsant, and antiamnesic activity [1 – 3]. This study was devoted to the search for new effective anxiolytics among 4-amino-2,6-dimethylnicotinic acid esters and amides. In the first step, 4-chloro-2,6-dimethylnicotinic acid ethylate (I) [4] reacted with the corresponding amines to yield 4-amino-2,6-dimethylnicotinic acid ethyl esters (IIa – IIf, III) in the form of bases or salts. Subsequent saponification of ethylate I led to acid IV, which was converted into 2,6-dimethylnicotinic acid amide (V) under the action of thionyl chloride and ammonia. Heating compound V with amines led to amides VI. The IR and H NMR spectra of the synthesized compounds (Table 1) agree with the proposed structures. The IR spectra if compounds IIa – IIc contain intense absorption bands due to carboethoxy groups at 1716 – 1695 cm – . In addition, the spectrum of compound IIc displays the stretching vibrations of free amino groups at 3341 and 3202 cm – . The H NMR spectra of compounds IIa – IIf, III, and VIb show the signals from 5-H protons of the pyridine cycle, 2and 6-methyl groups, and substituents in position 4. The proposed structures were also confirmed by the results of elemental analyses. The synthesized compounds were characterized with respect to anxiolytic activity in the conflict situation test.