Structural Exploration of (3S,6S)‐6‐Benzhydryl‐N‐benzyltetrahydro‐2H‐pyran‐3‐amine Analogues: Identification of Potent Triple Monoamine Reuptake Inhibitors as Potential Antidepressants

• DOI: 10.1002/cmdc.201200352
• Publication Date: 2012-10-11T15:58:38Z
• Authors: Soumava Santra; Sanjib Gogoi; Bhaskar Gopishetty; Tamara Antonio; Juan Zhen; Maarten E. A. Reith; Aloke K. Dutta
• Keywords: Norepinephrine transporter; Reuptake; Biogenic amine

Abstract To further explore the basic structural motifs (3 S ,6 )‐6‐benzhydryl‐ N ‐benzyltetrahydro‐2 H ‐pyran‐3‐amine and (2 ,4 R ,5 )‐2‐benzhydryl‐5‐(benzylamino)tetrahydro‐2 ‐pyran‐4‐ol, developed by our research group, for monoamine transport inhibition, we designed synthesized various structurally altered analogues. The new compounds were tested their affinities dopamine transporter (DAT), serotonin (SERT), norepinephrine (NET) in rat brain measuring capacity to inhibit uptake of [ 3 H]DA, H]5‐HT, H]NE, respectively. Our results point novel with a TUI, DNRI, SNRI, or SSRI profile. Among TUIs, compound 2 g exhibited balanced potency all three transporters ( K i : 60, 79, 70.3 n M DAT, SERT, NET, respectively). In forced swim test, produced significant decrease immobility drug‐treated rats relative vehicle, indicating potential antidepressant property.