Identification of 1‐phenoxy‐3‐(piperazin‐1‐yl)propan‐2‐ol derivatives as novel triple reuptake inhibitors

• Published in: Bulletin of the Korean Chemical Society Vol. 44; no. 7; pp. 596 - 599
• Main Authors: Ashrafuzzaman, Md, Ji, Su Hyun, Ahn, Hyomin, Chung, Hwan Won, Choi, Daeun, Park, Ju Jin, Go, Minji, Pyo, Jung In, Shafioul, Azam Sharif Mohammed, Lee, Duck‐Hyung, Chi, Sung‐Gil, Song, Chiman, Cheong, Chan Seong, Han, Seo‐Jung
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley‐VCH Verlag GmbH & Co. KGaA 01.07.2023; 대한화학회
• Subjects: antidepressants; aryloxypropanolpiperazine; major depressive disorder; monoamine neurotransmitter; triple reuptake inhibitor; 화학
• ISSN: 1229-5949; 0253-2964; 1229-5949
• DOI: 10.1002/bkcs.12693

Novel 1‐phenoxy‐3‐(piperazin‐1‐yl)propan‐2‐ol derivatives were designed and synthesized as potential triple reuptake inhibitors, which simultaneously inhibit serotonin, norepinephrine, and dopamine transporters (SERT, NET, and DAT, respectively). Through neurotransmitter transporter uptake assays, inhibitory activities of 1‐phenoxy‐3‐(piperazin‐1‐yl)propan‐2‐ol derivatives were evaluated. We discovered compound 19 exhibited the most potent inhibitory activities against all three monoamine neurotransmitter transporters and the IC50 values of 19 against SERT, NET, and DAT were determined. In addition, binding modes of 19 with SERT, NET, and DAT were predicted by docking studies. Novel 1‐phenoxy‐3‐(piperazin‐1‐yl)propan‐2‐ol derivatives exhibited potent inhibitory activities against serotonin, norepinephrine, and dopamine transporters (SERT, NET, and DAT, respectively) simultaneously and thus, 1‐phenoxy‐3‐(piperazin‐1‐yl)propan‐2‐ol derivatives possessed potential as triple reuptake inhibitors. Compound 19 possessed the most potent combination of SERT, NET, and DAT inhibitory activity with inhibition values greater than 60% for all three monoamine transporters.