scholarly journals Structural Determinants of Opioid Activity in Derivatives of 14-Aminomorphinones:  Effect of Substitution in the Aromatic Ring of Cinnamoylaminomorphinones and Codeinones

2006 ◽  
Vol 49 (17) ◽  
pp. 5333-5338 ◽  
Author(s):  
Nick P. R. Nieland ◽  
Humphrey A. Moynihan ◽  
Simon Carrington ◽  
Jillian Broadbear ◽  
James H. Woods ◽  
...  
Keyword(s):  
Aromatic Ring ◽  
Structural Determinants ◽  
Opioid Activity ◽  
Derivatives Of

scholarly journals Structural Determinants of Opioid Activity in Derivatives of 14-Aminomorphinones:  Effects of Changes to the Chain Linking of the C14-Amino Group to the Aryl Ring

2006 ◽  
Vol 49 (20) ◽  
pp. 6104-6110 ◽  
Author(s):  
David Rennison ◽  
Humphrey Moynihan ◽  
John R. Traynor ◽  
John W. Lewis ◽  
Stephen M. Husbands
Keyword(s):  
Amino Group ◽  
Structural Determinants ◽  
Opioid Activity ◽  
Aryl Ring ◽  
Derivatives Of

scholarly journals Derivatives of the β-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1307 ◽  
Author(s):  
Eliška Kohelová ◽  
Rozálie Peřinová ◽  
Negar Maafi ◽  
Jan Korábečný ◽  
Daniela Hulcová ◽  
...  
Keyword(s):  
Active Sites ◽  
Glycogen Synthase ◽  
Binding Modes ◽  
Structural Determinants ◽  
Inhibitory Potential ◽  
Gsk 3Β ◽  
Inhibition Potency ◽  
Derivatives Of ◽  
In Vitro Data

Twelve derivatives 1a–1m of the β-crinane-type alkaloid haemanthamine were developed. All the semisynthetic derivatives were studied for their inhibitory potential against both acetylcholinesterase and butyrylcholinesterase. In addition, glycogen synthase kinase 3β (GSK-3β) inhibition potency was evaluated in the active derivatives. In order to reveal the availability of the drugs to the CNS, we elucidated the potential of selected derivatives to penetrate through the blood-brain barrier (BBB). Two compounds, namely 11-O-(2-methylbenzoyl)-haemanthamine (1j) and 11-O-(4-nitrobenzoyl)-haemanthamine (1m), revealed the most intriguing profile, both being acetylcholinesterase (hAChE) inhibitors on a micromolar scale, with GSK-3β inhibition properties, and predicted permeation through the BBB. In vitro data were further corroborated by detailed inspection of the compounds’ plausible binding modes in the active sites of hAChE and hBuChE, which led us to provide the structural determinants responsible for the activity towards these enzymes.

Structural Determinants of Opioid Activity in the Orvinols and Related Structures:  Ethers of Orvinol and Isoorvinol

2000 ◽  
Vol 43 (9) ◽  
pp. 1852-1857 ◽  
Author(s):  
Andrew Coop ◽  
Claire L. Norton ◽  
Ilona Berzetei-Gurske ◽  
Jackie Burnside ◽  
Lawrence Toll ◽  
...  
Keyword(s):  
Structural Determinants ◽  
Opioid Activity

scholarly journals Potent Antiplasmodial Derivatives of the Antitussive Drug Dextromethorphan Reveal the Ent-Morphinan Pharmacophore of Tazopsine-Type Alkaloids

2022 ◽  
Author(s):  
Antoinette Keita ◽  
Jean-François Franetich ◽  
Maelle Carraz ◽  
Loise Valentin ◽  
Mallaury Bordesoulles ◽  
...  
Keyword(s):  
Fold Increase ◽  
Structural Determinants ◽  
Prophylactic Drugs ◽  
Therapeutic Development ◽  
Ic50 Values ◽  
Phase Selectivity ◽  
Definition Of ◽  
Further Development ◽  
Derivatives Of

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

A Study of Reactivity of Model Compounds of Lignin Biopolymer

2021 ◽  
Vol 316 ◽  
pp. 75-80
Author(s):  
Oleg Kh. Karimov ◽  
Galina Yu. Kolchina ◽  
Eldar M. Movsumzade
Keyword(s):  
Aromatic Ring ◽  
Quantum Chemical ◽  
Density Functional ◽  
Nucleophilic Attack ◽  
Hydroxyl Group ◽  
Model Compounds ◽  
Hartree Fock ◽  
Quantitative Characteristics ◽  
Derivatives Of ◽  
Hybrid Density Functional

In the framework of method of the B3LYP hybrid density functional and the restricted Hartree-Fock method, quantum-chemical calculations of model compounds of lignin, i.e. derivatives of p-hydroxycinnamic alcohol were carried out. The structures and reactivity of coumaric, coniferyl and synapol alcohols were studied. Quantitative characteristics of the reactivity of these acids are given. It is found that the electronic structure of lignin is determined primarily by the charge distribution in its structural phenylpropane unit. In the molecules of all model compounds of lignin, the center for nucleophilic attack is the carbon of aromatic ring (E-ring) with a hydroxyl group, and in the molecule of synapol alcohol, this center is also the carbon of the aromatic ring (E-ring) with a methoxy group. In all three compounds, a center with an increased electron density appears on the Сβ carbon atom.

Chemistry of the Podocarpaceae. XXXII. Stereochemistry of 6-Bromo-7-oxo derivatives of ring-c aromatic diterpenoids

1971 ◽  
Vol 24 (6) ◽  
pp. 1237 ◽  
Author(s):  
RC Cambie ◽  
DR Crump ◽  
WA Denny ◽  
TJ Fullerton
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Aromatic Ring ◽  
Nuclear Overhauser Effect ◽  
Optical Rotatory Dispersion ◽  
Optical Rotatory ◽  
Effect Data ◽  
Overhauser Effect ◽  
Methoxycarbonyl Group ◽  
Nuclear Overhauser ◽  
Derivatives Of

The stereochemistry of 6-bromo-7-oxo derivatives of diterpenoids possessing an aromatic ring c is discussed. Nan-stereospecific bromination of 7-oxo diterpenoids occurs for compounds with an unactivated aromatic ring provided that no methoxycarbonyl substituent is at C 4. It also occurs for a C 19 acetate providing an activating substituent is present at C 12, but not for compounds with a C 4 methoxycarbonyl group even if they possess a C 12 activating substituent. The assignment of configuration of 6-bromo substituents from nuclear magnetic resonance and nuclear Overhauser effect data is examined and limitations to the use of optical rotatory dispersion curves are discussed.

scholarly journals Profiling the structural determinants of aminoketone derivatives as hNET and hDAT reuptake inhibitors by field-based QSAR based on molecular docking

2021 ◽  
Vol 29 ◽  
pp. 257-273
Author(s):  
Panpan Wang ◽  
Chenxi Jing ◽  
Pei Yu ◽  
Meng Lu ◽  
Xiaobo Xu ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Medicinal Chemistry ◽  
Structural Features ◽  
Clinical Settings ◽  
Training Set ◽  
Structural Determinants ◽  
Test Set ◽  
Contour Maps ◽  
Pharmacokinetic Properties ◽  
Derivatives Of

BACKGROUND: Bupropion, one of the dual norepinephrine and dopamine reuptake inhibitors (NDRIs), is an aminoketone derivative performed effect in improving cognitive function for depression. However, its therapeutic effect is unsatisfactory due to poor clinical response, and there are only few derivatives in pre-clinical settings. OBJECTIVE: This work attempted to elucidate the essential structural features for the activity and designed a series of novel derivatives with good inhibitive ability, pharmacokinetic and medicinal chemistry properties. METHODS: The field-based QSAR of aminoketone derivatives of two targets were established based on docking poses, and the essential structural properties for designing novel compounds were supplied by comparing contour maps. RESULTS: The selected two models performed good predictability and reliability with R2 of 0.8479 and 0.8040 for training set, Q2 of 0.7352 and 0.6266 for test set respectively, and the designed 29 novel derivatives performed no less than the highest active compound with good ADME/T pharmacokinetic properties and medicinal chemistry friendliness. CONCLUSIONS: Bulky groups in R1, bulky groups with weak hydrophobicity in R3, and potent hydrophobic substituted group with electronegative in R2 from contour maps provided important insights for assessing and designing 29 novel NDRIs, which were considered as candidates for cognitive dysfunction with depression or other related neurodegenerative disorders.

Three trithiadiazepines and a trithiatriazepine

2013 ◽  
Vol 70 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Ray Jones
Keyword(s):  
Electron Density ◽  
Aromatic Ring ◽  
Intermolecular Interactions ◽  
Experimental Studies ◽  
Asymmetric Unit ◽  
Effect Of Substituents ◽  
Deformation Density ◽  
Density Analysis ◽  
Derivatives Of ◽  
Bonding Electron

The structures of 6-nitro-1,3λ4δ2,5,2,4-trithiadiazepine [C2HN3O2S3, (1)], 6,7-dinitro-1,3λ4δ2,5,2,4-trithiadiazepine [C2N4O4S3, (2)], 1,3λ4δ2,5,2,4-trithiadiazepine-6,7-dicarbonitrile [C4N4S3, (3)] and 7-acetyl-1,3λ4δ2,5,2,4,6-trithiatriazepine [C3H3N3OS3, (4)] presented here include the most precise determinations of these seven-membered 10 π-electron aromatic ring systems published to date. Both (2) and (3) are sited around crystallographic twofold axes with half a molecule per asymmetric unit. Comparison with other published derivatives of these rings reveals the effect of substituents on bonding, conformations and intermolecular interactions, including π-stacking. The deformation density analysis of (2) is consistent with the expected bonding electron density from other theoretical and experimental studies.

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