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In accordance to this drift, herein we describe the design and synthesis of a set of new heterocyclic analogs consisting of 6,7\u2010dimethyl Quinoxaline, appended to a connector, employing Schiff base strategy (Compounds <jats:bold>I<\/jats:bold>\u2013<jats:bold>IX<\/jats:bold>). The compounds were characterized by various spectroscopic techniques and the kinase inhibition assay were performed on few prime members of the CMGC family namely the GSK3\u03b2, DYRK1A and CLK1 receptors, respectively, that have been known to be directly involved in hyperphosphorylation of Tau. Interestingly the biological evaluation results revealed that Compounds <jats:bold>IV<\/jats:bold> and <jats:bold>V<\/jats:bold>, with bromo\/chloro functionalities in the aromatic core were advantaged of being highly selective towards the target GSK3\u03b2 over others. To strengthen our analysis, we adopted molecular modelling studies, where compounds <jats:bold>IV\/V<\/jats:bold> were redocked in the same grid 4AFJ, as that of the reference ligand, 5\u2010aryl\u20104\u2010carboxamide\u20101,3\u2010oxazole. Surprisingly, our investigation underpinned that for both the compounds <jats:bold>IV\/V<\/jats:bold>, a primary H\u2010bonding existed between the designed molecules (<jats:bold>IV\/V<\/jats:bold>) and Val 135 residue in the receptor GSK3\u03b2, in line with the reference ligand. We attribute this interaction to instigate potency in the compounds. Indeed the other non\u2010covalent interaction, between the derivative's aromatic nucleus and Arg 141\/Thr 138 in the receptor GSK3\u03b2, might have been responsible for enhancing the selectivity in the targets. Overall, we feel that the present work depicts a logical demonstration towards fine tuning the efficacy of the inhibitors through systematic adjustment of electron density at appropriate positions in the aromatic ring be it the main quinoxaline or the other aromatic nucleus. Thus this pathway offers a convenient strategy for the development of efficient therapeutics for diversified neurodegenerative diseases like that of Alzheimer's.<\/jats:p>","DOI":"10.1002\/cbdv.202100364","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T02:27:02Z","timestamp":1630895222000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Unravelling the Selectivity of 6,7\u2010Dimethyl Quinoxaline Analogs for Kinase Inhibition: An Insight towards the Development of Alzheimer's Therapeutics"],"prefix":"10.1002","volume":"18","author":[{"given":"Arvind","family":"Kumar Jain","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Rajiv Gandhi Technological University  Bhopal 462033 Madhya Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arindam","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry IISER Bhopal  Bhopal 462066 Madhya Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Karthikeyan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Indira Gandhi National Tribal University  Amarkantak (MP) 484887 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piyush","family":"Trivedi","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Rajiv Gandhi Technological University  Bhopal 462033 Madhya Pradesh India"},{"name":"Center of Innovation and Translational Research, BharatiVidyapeeth  Pune 411038, Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Dutt Konar","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Rajiv Gandhi Technological University  Bhopal 462033 Madhya Pradesh India"},{"name":"Dept. of Applied Chemistry Rajiv Gandhi Technological University, Bhopal  Bhopal 462033 Madhya Pradesh India"},{"name":"University Grants Commission, New Delhi \u2013  110002 New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"e_1_2_7_1_1","first-page":"146","article-title":"\u2018Allgemeine Zeitschrift f\u00fcr Psychiatrie und Psychisch-Gerichtliche Medizin\u2019","volume":"64","author":"Alzheimer A.","year":"1907","journal-title":"Alzforum"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.111"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2012.06.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145007"},{"key":"e_1_2_7_5_1","unstructured":"F. 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