Synthesis, Neurotropic Activity, and Molecular Docking of New Condensed Thieno[2,3-b]pyridine Derivatives

• Published in: Russian journal of bioorganic chemistry 2022-02, Vol.48 (1), p.125-134
• Main Authors: Dabaeva, V. V., Baghdasaryan, M. R., Paronikyan, R. G., Nazaryan, I. M., Hakobyan, H. G., Hunanyan, L. S., Paronikyan, E. G., Dashyan, Sh. Sh
• Format: Article
• Language: English
• Subjects: Anticonvulsants; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Chemical synthesis; Life Sciences; Molecular docking; Organic Chemistry; Pyrimidines; Receptors; Substitution reactions
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162022010034

Methods for the preparation of new condensed derivatives of pyrido[3',2':4,5]thieno[3,2- d ]pyrimidines based on 5,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile were developed. Substitution reactions in the 3rd and 4th positions of 7,8-dimethylpyrido[3',2':4,5]thieno[3,2- d ]pyrimidin-4(3 H )-one were conducted. The neurotropic activity of 12 obtained compounds was studied in vivo in rats and mice. Eight compounds were found to have an anticonvulsant effect of antagonism with corazole. Four selected compounds had anxiolytic and behavior activating effects. Molecular docking of the synthesized compounds was performed to predict their interaction with the GABA A receptor. Five compounds were identified, the complexation of which with the GABA A receptor occurs in two places: the benzamidine site of subsite 1 and subsite 3 of the ECD interface, which indicates the inhibitory effect of the compounds on the target.