Han, Minsoo Song, Chiman Jeong, Nakcheol Hahn, Hoh-Gyu 2024-01-20T09:02:38Z 2024-01-20T09:02:38Z 2021-09-02 2014-09 1948-5875 https://pubs.kist.re.kr/handle/201004/126422 For a development of broad spectrum antidepressant 3-aminoazetidine derivatives, two series of compounds were explored by bioisosteric modification of 3-a-oxyazetidine. We synthesized 166 novel 3-aminoazetidine derivatives in series A and B, starting from Boc-protected 3-azetidinone (3) and Boc-protected 3-azetidinal (9) respectively, through parallel syntheses. The inhibitory reuptake activities against serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmitters were measured by the Neurotransmitter Transporter Uptake Assay Kit using the human embryonic kidney 293 (HEK293) cells stably transfected with the respective three kinds of human transporters (hSERT, hNET, and hDAT). Our study aimed to identify compounds having relative inhibitory activities against hSERT > hNET > hDAT. Lead optimization including microsomal stability, CYP, hERG assay, Ames test, BBB, and PK study resulted in the identification of compound 10dl as a candidate for further studies. English AMER CHEMICAL SOC MAJOR DEPRESSIVE DISORDER DRUG DESIGN BUPROPION SEROTONIN COMBINATION STRATEGIES DOPAMINE Exploration of 3-Aminoazetidines as Triple Reuptake Inhibitors by Bioisosteric Modification of 3-alpha-Oxyazetidine Article 10.1021/ml500187a 1 ACS MEDICINAL CHEMISTRY LETTERS, v.5, no.9, pp.999 - 1004 ACS MEDICINAL CHEMISTRY LETTERS 5 9 999 1004 scie scopus 000341619800009 2-s2.0-84907506775 Chemistry, Medicinal Pharmacology & Pharmacy Article MAJOR DEPRESSIVE DISORDER DRUG DESIGN BUPROPION SEROTONIN COMBINATION STRATEGIES DOPAMINE Depression triple reuptake inhibitor 3-aminoazetidines biososterism