Azepines and Piperidines with Dual Norepinephrine Dopamine Uptake Inhibition and Antidepressant Activity

Brown, Dean G.; Bernstein, Peter R; Wu, Ye; Urbanek, Rebecca A.; Becker, Christopher; Throner, Scott; Dembofsky, Bruce T.; Steelman, Gary B.; Lazor, Lois Ann; Scott, Clay W.; Wood, Michael W.; Wesolowski, Steven S.; Nugiel, David A.; Koch, Stephanie; Yu, Ji-Guo; Pivonka, Donald E.; Li, Shuang; Thompson, Carol; Zacco, Anna; Elmore, Charles S.; Schroeder, Patricia; Liu, Jianwei; Hurley, Christopher A.; Ward, Stuart I.; Hunt, Hazel; Williams, Karen; McLaughlin, Joseph; Hoesch, Valerie; Sydserff, S G; Maier, Donna L.; Aharony, David

doi:10.1021/ml300262e

Cited by 26 publications

(9 citation statements)

References 23 publications

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“…In agreement with the reported results,11 a nitro group was reduced to an amino group (Table 2, entry 7). Notably, concomitant reductions of ester group on an arene to methyl rather than hydroxymethyl (entries 9 and 25) and alkene to alkane (entry 12) are not readily achieved by other methods, and may find application in some multistep synthesis 5c,i. Although secondary and tertiary amides were reduced at room temperature, the reduction of primary amides and lactam was best conducted at 0 °C (Table 2, entries 19, 33–36).…”

Section: Methodsmentioning

confidence: 99%

Structural, Vibrational and Electronic Properties of Defective Single‐Walled Carbon Nanotubes Functionalised with Carboxyl Groups: Theoretical Studies

2015

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Covalent sidewall functionalisation of defective zigzag single-walled carbon nanotubes [SWCNTs(10,0)] with COOH groups is investigated by using DFT. Four types of point defects are considered: vacancy (V), divacancy [V (5-8-5), V (555-777)], adatom (AA) and Stone-Wales (SW). The energetic, structural, electronic and vibrational properties of these systems are analysed. Decreasing reactivity is observed in the following order: AA>V>V (555-777)>V (5-8-5)>SW. These studies also demonstrate that the position in which a carboxyl group is attached to a defective SWCNT is of primary importance. Saturation of two-coordinate carbon atoms in systems with the vacancy V-7 and with the adatom AA-1(2) is 3.5-4 times more energetically favourable than saturation of three-coordinate carbon atoms for all studied systems. Vibrational analysis for these two systems shows significant redshifts of the ν(CO) stretching vibration of 96 and 123 cm compared to that for carboxylated pristine systems. Detailed electronic-structure analysis of the most stable carboxylated systems is also presented.

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Section: Methodsmentioning

confidence: 99%

Structural, Vibrational and Electronic Properties of Defective Single‐Walled Carbon Nanotubes Functionalised with Carboxyl Groups: Theoretical Studies

2015

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“…Access to seven‐membered ring systems, especially seven‐membered N ‐heterocyclic systems, have gained growing interest among the synthetic community owing to the continuing identification of the seven‐membered‐ring‐containing natural products with the appealing pharmacological and pesticidal activities . Attractive N ‐heterocyclic systems include azepine derivatives, which are unique structural motifs presented in many biologically active natural products and pharmaceuticals, such as balanol,, capuramycin and its derivatives, (−)‐cobactin T,– tuberocrooline,, (−)‐stemoamide,– and ( S )‐3‐(3,4‐dichlorophenyl)‐2,3,4,7‐tetrahydro‐1 H ‐azepine (Scheme ). Accordingly, considerable efforts has been devoted to the development of new efficient methods for assembling azepines .…”

Section: Methodsmentioning

confidence: 99%

[5+2] Cycloaddition of 2‐(2‐Aminoethyl)oxiranes with Alkynes via Epoxide Ring‐Opening: A Facile Access to Azepines

Song

et al. 2016

Angewandte Chemie

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A new FeCl3 and BF3⋅OEt2 co‐catalyzed tandem hetero‐[5+2] cycloaddition of 2‐(2‐aminoethyl)oxiranes with a wide range of alkynes, including terminal alkynes and alkyl‐substituted internal alkynes is presented. This is the first example of rapid and facile production of diverse 2,3‐dihydro‐1H‐azepines through a sequence of epoxide ring‐opening, annulation, and dehydroxylation with broad substrate scope and exquisite selectivity control.

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“…[ 136 ] Thus, Brown's group explored, designed, and synthesized 2,3,4,7‐tetrahydro‐1 H ‐azepine derivatives and piperidine analogues with azepine moiety to avoid this side effect. [ 137 ] Two compounds, 75 and 76 , ( Figure ) provided good affinity for NET and DAT with K i values of 17, 6.0 × 10 −9 m and 4.0, 6.0 × 10 −9 m , respectively, and demonstrated antidepressant effect similar to Nomifensine in the FST at doses of 3 and 7.3 mg kg −1 (i.p. ), respectively.…”

Section: Advances In Small Molecules With Antidepressant Activitiesmentioning

confidence: 99%

Antidepressant Drug Discovery and Development: Mechanism and Drug Design Based on Small Molecules

Yao

Jiang

et al. 2022

Advanced Therapeutics

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Depression is one of the most prevalent mental diseases and a primary cause of disability worldwide with high incidence and high recurrence. The current deterioration of the COVID‐19 epidemic also pushes up the incidence of depression. Nevertheless, the currently available treatments remain inadequate response and limited efficacy. Therefore, discoveries of more potent and safer antidepressant drugs are urgently needed. In this review, the current potential physiological and pathological mechanisms of depression, and the clinical research progresses of candidate drugs as well as the recent advances in small‐molecule drug discovery for potential treatments of depression are systematically summarized. More importantly, the structure–activity relationships of compounds from different classes, the statistical analysis of the blood‐brain barrier permeability, the pharmacological targets, and the in vivo models are comprehensively discussed. Further insights on antidepressant drug discovery are also analyzed from multidimensional perspectives.

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Azepines and Piperidines with Dual Norepinephrine Dopamine Uptake Inhibition and Antidepressant Activity

Cited by 26 publications

References 23 publications

Structural, Vibrational and Electronic Properties of Defective Single‐Walled Carbon Nanotubes Functionalised with Carboxyl Groups: Theoretical Studies

Structural, Vibrational and Electronic Properties of Defective Single‐Walled Carbon Nanotubes Functionalised with Carboxyl Groups: Theoretical Studies

[5+2] Cycloaddition of 2‐(2‐Aminoethyl)oxiranes with Alkynes via Epoxide Ring‐Opening: A Facile Access to Azepines

Antidepressant Drug Discovery and Development: Mechanism and Drug Design Based on Small Molecules

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