Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

Ramesh, B.; Baby, C.; Moni, M. S.; Subramanian, K. G.

doi:10.1016/j.molstruc.2013.02.029

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…However, it is also noted that ring conformational changes leading to observed broadening have been reported in piperazines and morpholines. 26,27 In morpholines, these conformational changes take on the form of ring inversions, which agrees better with the data presented in Figure 5, showing that only 12 and 15 display exchange broadening where 13 and 14 do not.…”

Section: ■ Experimental Methodssupporting

confidence: 90%

Kinetics of Formation of Quantum Dot Solvent N-Oleoylmorpholine

Webster

Lugo-Pimentel

Kretzschmar

et al. 2020

Ind. Eng. Chem. Res.

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The kinetics of the synthesis of noncommercially available quantum dot (QD) solvent N-oleoylmorpholine (NOM) was investigated in a semibatch reactor system to enable scale up. Morpholine was injected into excess oleic acid (OA) at rates of 250 and 500 μL/h at 110, 140, and 170 °C. The reaction was found to be zero order in morpholine, first order in OA, and first order overall for temperatures ≥140 °C. At < 140 °C, the reaction does not follow elementary kinetics with respect to OA. Thermodynamic calculations using the Eyring−Polyani equation determined that the entropy change from the reagents to the transition state was negative, suggesting an associative complex intermediate species. The reaction mechanism was further analyzed via IR and NMR, revealing a carboxyl−amino intermediate, which was long lived (>1 h) at 110 °C but short lived (<30 min) at 170 °C. Conversions of 85% to near completion are achievable for OA, and excess morpholine was removed via rotary evaporation, thus yielding NOM with 70−98% purity.

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Section: ■ Experimental Methodssupporting

confidence: 90%

Kinetics of Formation of Quantum Dot Solvent N-Oleoylmorpholine

Webster

Lugo-Pimentel

Kretzschmar

et al. 2020

Ind. Eng. Chem. Res.

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“…In the present case, this process is also decreased at room temperature (splitting of the NCH 2 signals at the amine nitrogen atom). For simple non-acylated piperazines 42–44 and morpholines 45 the observation of distinct conformers by NMR is restricted to low temperatures (<−10 °C). The different energy barriers of both effects resulted in two different coalescence points.…”

Section: Resultsmentioning

confidence: 99%

NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution

et al. 2018

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“…Also, it can be added to enhance the potency toward a target protein, as the oxygen atom can form hydrogen bonds, while the relatively electron-deficient ring can establish hydrophobic interactions . Finally, the flexible conformation resulting from the equilibrium between the chairlike and skew-boat topologies provides the optimal features for a suitable scaffold directing the appendages in the right position. , Morpholine has also an improved CYP3A4 profile, prolonged bioavailability, and optimal clearance, being oxidized easily into nontoxic derivatives. − A plethora of morpholine derivatives have already been present in the market for several decades (Figure ). Just to give some examples, doxapram (1976), phendimetrazine (1979), moclobemide (1992), reboxetine (1997), and aprepitant (2003) − are drugs with applications in several CNS diseases, mainly as anxiolytics and/or antidepressants.…”

Section: Introductionmentioning

confidence: 99%

Occurrence of Morpholine in Central Nervous System Drug Discovery

Lenci

Calugi

Trabocchi

2021

ACS Chem. Neurosci.

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Developing drugs for the central nervous system (CNS) requires fine chemical modifications, as a strict balance between size and lipophilicity is necessary to improve the permeability through the blood-brain barrier (BBB). In this context, morpholine and its analogues represent valuable heterocycles, due to their conformational and physicochemical properties. In fact, the presence of a weak basic nitrogen atom and of an oxygen atom at the opposite position provides a peculiar pK a value and a flexible conformation to the ring, thus allowing it to take part in several lipophilic−hydrophilic interactions, and to improve blood solubility and brain permeability of the overall structure. In CNS-active compounds, morpholines are used (1) to enhance the potency through molecular interactions, (2) to act as a scaffold directing the appendages in the correct position, and (3) to modulate pharmacokinetic/ pharmacodynamic (PK/PD) properties. In this perspective, selected morpholinecontaining CNS drug candidates are discussed to reveal the active pharmacophores accountable for the (1) modulation of receptors involved in mood disorders and pain, (2) bioactivity toward enzymes and receptors responsible for neurodegenerative diseases, and (3) inhibition of enzymes involved in the pathology of CNS tumors. The medicinal chemistry/pharmacological activity of morpholine derivatives is discussed, in the effort to highlight the importance of morpholine ring interactions in the active site of different targets, particularly reporting binding features retrieved from PDB data, when available.

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Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

Cited by 9 publications

References 21 publications

Kinetics of Formation of Quantum Dot Solvent N-Oleoylmorpholine

Kinetics of Formation of Quantum Dot Solvent N-Oleoylmorpholine

NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution

Occurrence of Morpholine in Central Nervous System Drug Discovery

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