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Among all the synthesized compounds, compound <jats:bold>5<\/jats:bold> (3\u2010methyl\u20106\u2010phenyl\u20102\u2010(piperazin\u20101\u2010yl)\u20103,4\u2010dihydropyrimidin\u20104\u2010one) exhibited the most potent inhibitory activity against <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103<jats:italic>\u03b2<\/jats:italic> with <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> value of 74 n<jats:sc>m<\/jats:sc>. The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val\u2010135 to the active site of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103<jats:italic>\u03b2<\/jats:italic> was observed. Furthermore, the synthesized compounds were subjected to <jats:italic>in vivo<\/jats:italic> evaluation of their antidepressant activity, and compound <jats:bold>5<\/jats:bold> showing highest inhibition of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103<jats:italic>\u03b2<\/jats:italic> was also found to significantly reduce the duration of immobility at 50 mg\/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound <jats:bold>5<\/jats:bold> may serve as a valuable template for the design and development of inhibitors of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103<jats:italic>\u03b2<\/jats:italic> with antidepressant activity.<\/jats:p>","DOI":"10.1111\/cbdd.12710","type":"journal-article","created":{"date-parts":[[2015,12,30]],"date-time":"2015-12-30T10:49:07Z","timestamp":1451472547000},"page":"764-772","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis of Novel Pyrimidin\u20104\u2010One Bearing Piperazine Ring\u2010Based Amides as Glycogen Synthase Kinase\u20103<i>\u03b2<\/i> Inhibitors with Antidepressant Activity"],"prefix":"10.1111","volume":"87","author":[{"given":"Imran","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Chemistry Faculty of Science Hamdard University New Delhi 110 062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mushtaq A.","family":"Tantray","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science Hamdard University New Delhi 110 062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hinna","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science Hamdard University New Delhi 110 062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Sarwar","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science Hamdard University New Delhi 110 062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abul","family":"Kalam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Hamdard University New Delhi 110 062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faraz","family":"Shaikh","sequence":"additional","affiliation":[{"name":"National Facility for Drug Discovery Department of Chemistry Saurashtra University Gujarat 360005 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anamik","family":"Shah","sequence":"additional","affiliation":[{"name":"National Facility for Drug Discovery Department of Chemistry Saurashtra University Gujarat 360005 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Firasat","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science University of Delhi New Delhi 110 062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,2,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11902-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07419.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35096075"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201463v"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2111"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69113-7"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8455"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.789"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(03)00206-2"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0721327.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2002.40201.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000494"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450110607011421"},{"key":"e_1_2_6_15_1","first-page":"76","volume-title":"The Neurobiology of Bipolar Disorder. 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