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According to the results of the EPM, four active compounds were found in 2a, 2b, 2c, 4b. Their anxiolytic properties were confirmed in terms of LDB and the most active was compound 2b. In the OF, only 2c had an influence on the locomotor activity of the rodents. Thus, the most promising substance was determined; this was 2b, which has the structure of 2-(2-{[3-(4-tert-butylphenyl)quinoxaline-2-yl]methyl}-4,5-dimethoxyphenyl)-N-methylethan-1-amine hydrochloride. The obtained data were analyzed with the pharmacophore feature prediction approach, which made it possible to compare the structures of the studied compounds with the reference drug diazepam, and to determine the contribution of pharmacophores to the manifestation of the activity under study. ADMET analysis was carried out for compound 2b and the acute oral toxicity of this substance was also tested in vivo. As a result of the study, a promising compound with a high anxiolytic effect and low level of toxicity 2b was found, which is of interest for further preclinical study of its properties.<\/jats:p>","DOI":"10.3390\/ijms232214401","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:05:11Z","timestamp":1668999911000},"page":"14401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, Synthesis and Pharmacological Evaluation of Novel C2,C3-Quinoxaline Derivatives as Promising Anxiolytic Agents"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-6621","authenticated-orcid":false,"given":"Dmitriy V.","family":"Maltsev","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"},{"name":"Volgograd Medical Research Center, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria O.","family":"Skripka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"},{"name":"Volgograd Medical Research Center, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-4826","authenticated-orcid":false,"given":"Alexander A.","family":"Spasov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"},{"name":"Volgograd Medical Research Center, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-5052","authenticated-orcid":false,"given":"Pavel M.","family":"Vassiliev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"},{"name":"Volgograd Medical Research Center, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim A.","family":"Perfiliev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-0797","authenticated-orcid":false,"given":"Lyudmila N.","family":"Divaeva","sequence":"additional","affiliation":[{"name":"Research Institute of Physical and Organic Chemistry, Southern Federal University, 105\/42 Bolshaya Sadovaya Str., 344090 Rostov-on-Don, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Zubenko","sequence":"additional","affiliation":[{"name":"North-Caucasian Zonal Research Veterinary Institute, 346406 Novocherkassk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatolii S.","family":"Morkovnik","sequence":"additional","affiliation":[{"name":"Research Institute of Physical and Organic Chemistry, Southern Federal University, 105\/42 Bolshaya Sadovaya Str., 344090 Rostov-on-Don, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander I.","family":"Klimenko","sequence":"additional","affiliation":[{"name":"North-Caucasian Zonal Research Veterinary Institute, 346406 Novocherkassk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail V.","family":"Miroshnikov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladlen G.","family":"Klochkov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura R.","family":"Ianalieva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, 1 Pavshikh Bortsov sq., 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11920-019-0997-0","article-title":"Global Burden of Disease and the Impact of Mental and Addictive Disorders","volume":"21","author":"Rehm","year":"2019","journal-title":"Curr. 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