Morpholine as ubiquitous pharmacophore in medicinal chemistry: Deep insight into the structure-activity relationship (SAR)

Kumari, Archana; Singh, Rajesh

doi:10.1016/j.bioorg.2020.103578

Cited by 116 publications

(59 citation statements)

References 185 publications

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“…From these four leading compounds, CHEMBL1940937 has the highest vina score, which could be due to the carboxamide group that helps form hydrogen bonds easily. On the other hand, CHEMBL3900791 and CHEMBL3233752 both share a morpholine ring, which is related to several pharmacological activities [29]. The isoxazole group is also present on CHEMBL64623, a CCK-B antagonist.…”

Section: Ligand-based Chembl Database Screeningmentioning

confidence: 99%

Ligand-Based and Structured-Based In Silico Repurposing Approaches to Predict Inhibitors of SARS-CoV-2 Mpro Protein

et al. 2020

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a coronavirus that causes the pandemic Coronavirus Disease 2019 (COVID-19). There is no current specific treatment for this new coronavirus. In this study, we employed a virtual screening repurposing strategy to search for potential SARS-CoV-2 Mpro inhibitors. The databases PDB, ChEMBL, BindingDB and DrugBank were queried with several filtering steps based on ligand-based and structure-based approaches. As a result, we obtained 58 molecules (37 from ChEMBL and 21 from DrugBank) that potentially inhibit SARS-CoV-2 Mpro. These molecules have on their chemical structure functional groups that favor stronger docking scores than the inhibitor N3. Several of these molecules are reported experimentally as SARS-CoV Mpro inhibitors. Hence, a combined virtual screening strategy allowed finding chemical compounds with a high potential for the inhibition of SARS-CoV-2 Mpro.

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Section: Ligand-based Chembl Database Screeningmentioning

confidence: 99%

Ligand-Based and Structured-Based In Silico Repurposing Approaches to Predict Inhibitors of SARS-CoV-2 Mpro Protein

et al. 2020

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“…These H-bonding interactions are significant in downriver signifying routes in the literature. [27,28] The ArBTU derivative 3 g docking complexes have been explained as a graphical illustration (Figure 4). All the ligands in the active sites of AChE showed binding with similar interactive behavior and conformational.…”

Section: Structure-activity Relationship (Sar) Study Of Arbtu Derivatives With Achementioning

confidence: 99%

Pharmacokinetics, Mechanism, and Docking Study of Antioxidant Aryl‐Bisthiourea Derivatives for Alzheimer's Disease

et al. 2021

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Novel aryl-bisthiourea derivatives (3 a-3 j) were synthesized by a two-step route for the study of free-radical scavenging property and acetylcholinesterase enzyme (AChE) inhibition study. The effect of the electronic environment on the aryl structure of ArBTU on the AChE inhibition was studied. Lineweaver-Burk plot was used for kinetic study of inhibition of AChE by using ArBTU derivatives which exhibited very good bioactivity of inhibition against acetylcholinesterase enzyme. Central Nervous System (CNS) permeability and the Blood-Brain Barrier values of all ArBTU derivatives (3 a-3 j) were also similar to the reference value (> À 2 logPS < À 3 and > À 0.3 log BB < À 1), respectively. The molecular docking study of derivative 3 g presented a very good interactions with tested protein. The mechanism of AChE inhibition was found from the kinetic studies of novel ArBTU derivatives. A pharmacokinetic study of AChE inhibition was also evaluated. ArBTU derivatives (3 a-3 j) exhibited the best lead-like potential. Molecular docking study described the binding ability of the highly effective derivative 3 g with the acetylcholinesterase enzyme.

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“…[1c-d,4] Appearently, morpholine moiety is one of the key pharmacophores found in the structure of various marketed drugs and drug candidates including multisubstituted thiophenes. [1,5] Synthesis of 3-iodothiophenes from 1-mercapto-3yn-2-ols via iodocyclization method was first developed by Larock et.al.. [6] Then, the process could be also carried out in ionic liquids and deep eutectic solvents (DESs) without an external base (Scheme 1a). [7] Another approach to 3-iodothiophenes was provided with (Z)-thiobutenynes in the presence of iodine or CuSO 4 • 5H 2 O and NaI mixture which forms CuI 2 in situ (Scheme 1b).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 3‐Amino‐4‐iodothiophenes through Iodocyclization of 1‐(1,3‐Dithian‐2‐yl)propargylamines

et al. 2021

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1‐(1,3‐Dithian‐2‐yl)propargylamines undergo iodo‐cylization regioselectively to afford tetrasubstituted 3‐amino‐4‐iodothiophenes in 30–87 % yields by iodide induced cleavage of dithiane ring in a bicyclic sulfonium intermediate. A mechanism for this unprecedented transformation was proposed and tentatively supported by the isolation of an intermediate structure. 1‐(1,3‐Dithian‐2‐yl)propargylamines were prepared in 30–94 % yields by Au‐catalyzed one‐pot, three‐component reaction of 1,3‐dithiane‐2‐carbaldehydes, amines, and alkynes so called A3‐coupling reaction.

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Morpholine as ubiquitous pharmacophore in medicinal chemistry: Deep insight into the structure-activity relationship (SAR)

Cited by 116 publications

References 185 publications

Ligand-Based and Structured-Based In Silico Repurposing Approaches to Predict Inhibitors of SARS-CoV-2 Mpro Protein

Ligand-Based and Structured-Based In Silico Repurposing Approaches to Predict Inhibitors of SARS-CoV-2 Mpro Protein

Pharmacokinetics, Mechanism, and Docking Study of Antioxidant Aryl‐Bisthiourea Derivatives for Alzheimer's Disease

Synthesis of 3‐Amino‐4‐iodothiophenes through Iodocyclization of 1‐(1,3‐Dithian‐2‐yl)propargylamines

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