Design,synthesis, and biological activities of 1-aryl-1,4-diazepan-2-one derivatives as novel triple reuptake inhibitors |
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| Affiliation: | 2. Department of Inorganic Chemistry, Faculty of Science, Palacký University, 17.listopadu 12, CZ-771 46 Olomouc, Czech Republic;1. Steroid Hormones Section, NIDDK/LERB, National Institutes of Health, Bethesda, MD, United States;2. Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA, United States;1. Fakultät für Mathematik, Universität Bielefeld, Postfach 10 01 31, 33501 Bielefeld, Germany;2. The School of Computer Sciences, The Academic College of Tel-Aviv–Yaffo, 2 Rabenu Yeruham St., Tel-Aviv 61083, Israel;1. Institute of Developmental Biology, RAS, Vavilov Street, 26, 119334 Moscow, Russia;2. Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus;3. N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prospect, 47, 119991 Moscow, Russia;4. I. N. Ulyanov Chuvash State University, Moskovskiy pr., 15, 428015 Cheboksary, Russia;5. Department of Biological and Medicinal Chemistry, Moscow Institute of Physics and Technology, Institutsky Per. 9, Dolgoprudny, Moscow Region 141700, Russia;1. Martin-Luther Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;2. Chiroblock GmbH, Andresenstr. 1a, D-06766 Bitterfeld-Wolfen, Germany;1. Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China;2. Nuclear Medicine Department, Peking University 3rd Hospital, Beijing 100191, PR China |
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| Abstract: | A novel series of triple reuptake inhibitors were explored by ligand-based drug design. A cyclic structure was designed from cyclopropane derivative 5 using the core structure of reported monoamine reuptake inhibitors, leading to the formation of the 1-aryl-1,4-diazepan-2-one derivative 23j-S. Compound 23j-S was shown to act as a potent TRI with an excellent ADME-Tox profile. Oral administration of 23j-S significantly enhanced norepinephrine, dopamine, and serotonin levels in the mouse prefrontal cortex and showed significant antidepressant-like activity in tail suspension tests in mouse. |
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| Keywords: | Monoamine reuptake inhibition Triple reuptake inhibition 1-Aryl-1,4-diazepan-2-one compounds Tail suspension test Antidepressant |
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