Design,<i>in silico</i>studies, and synthesis of new 1,8-naphthyridine-3-carboxylic acid analogues and evaluation of their H1R antagonism effects

Gurjar, Vinod Kumar; Pal, Dilipkumar

doi:10.1039/d0ra00746c

Cited by 21 publications

(11 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Impetus, by the findings and less explored scaffold of 1,3‐dimethyl‐6‐amino‐5‐nitoso uracil and amides, herein, we successfully report a novel strategy for the synthesis of uracil‐based amide derivatives. The results obtained bypass the typical challenges in the synthesis of amides Over a decade, uracil and its derivatives have shown to exhibit antiviral and anticancer properties, which were proven both computationally as well as experimentally [21–24] . While newly discovered, 6‐amino‐1,3‐dimethyl uracil was shown to be used as an antioxidant agent [25] .…”

Section: Introductionmentioning

confidence: 86%

“…The results obtained bypass the typical challenges in the synthesis of amides Over a decade, uracil and its derivatives have shown to exhibit antiviral and anticancer properties, which were proven both computationally as well as experimentally. [21][22][23][24] While newly discovered, 6amino-1,3-dimethyl uracil was shown to be used as an antioxidant agent. [25] Majority of uracil derivatives are used as inhibitors of acetylcholinesterase (AchE) and butyrlcholinesterase (BuCHe), the key molecules involved in Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

et al. 2021

View full text Add to dashboard Cite

With the far-flung importance of uracil and amides in innumerable fields of chemistry and biology, a coherent synthesis that nullifies the use of prodigal reagents, methods and catalysts are hugely accepted. From the present outcomes, we report a highly atom profitable nucleophilic addition reaction of aromatic aldehydes and heterocyclic amines for the generation of amides having an excellent yield and high reproducibility. The main force responsible for the forward reaction is the presence of the nitroso group at the C-5 position on uracil scaffold, which drives the formation of formidable range products. The conclusive mechanism is based on the dehydrogenation reaction of the carbinolamine product formed during the nucleophilic addition reaction of the aromatic aldehyde with the free heterocyclic amino group to yield the corresponding amides. The synthesized compounds were predicated for biological properties and proved it to be an ideal G protein-coupled receptor kinase2 (GRK2) inhibitor. Out of all, the compound 3 f showed the most preeminent properties when compared to Paroxetine, studied using molecular docking. At the same time, computed ADME analysis proved them as an ideal drug candidate. Our findings not only prophesize new methods for the synthesis of bioactive-amides using a cross-coupling strategy but also demonstrates their novel applications as a human GRK2 inhibitor.

show abstract

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The PASS (Prediction of Activity Spectra for Substances, ((DOI: http://www.pharmaexpert.ru/PASSonline/predict.php) technique was used for statistical screening of possible biological effects, such as antihistaminic 34 and related behaviors, such as antiallergic, anti-asthmatic 35 , histamine release inhibition, rhinitis treatment, Immunomodulation, bronchodilation, and anti-IgE activities, anti-IL activity, PDE inhibition, anti-5HT3 activity, and so on. This software application created a mechanism for identifying an organic drug-like candidate's overall biological potential.…”

Section: Prediction Of Activity Spectra For Substances Testmentioning

confidence: 99%

Design, synthesis, and anti-bacterial activities of piperazine based phthalimide derivatives against superbug-Methicillin-Resistant Staphylococcus aureus

Prasad¹,

Ananda²,

Mukarambi³

et al. 2023

10.5267/j.ccl

View full text Add to dashboard Cite

A series of piperazine-based phthalimide derivatives 5 (a-l) were synthesized and extensively characterized using a variety of spectrum methods, including LC-MS, 1H-NMR, 13C-NMR, and FT-IR. All the derivatives were examined for their physicochemical, pharmacokinetic, bio-activity score, and PASS analysis. The 5e piperazine-based phthalimide derivative demonstrated promising antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in the in vitro antibacterial studies. In comparison to streptomycin and bacitracin (10 µg/mL), the minimum inhibitory concentration of 5e against MRSA was discovered to be 45±0.15 micro g/ml. The anti-MRSA activity was validated with membrane damage studies by using SEM, and in silico docking studies were against 3VMT and 6FTB proteins of MRSA. In the toxicity study, 5e derivatives were evaluated against L6 cell lines. The results of the studies show the synthesized 2-(2-(4-((4-chlorophenyl) sulfonyl) piperazin-1-yl) ethyl) isoindoline-1,3-dione (5e) can be used for the development of anti-MRSA drugs.

show abstract

“…Another study involving in silico design, synthesis, ADME profiling and evaluation of antagonistic effects of 1,8-naphthyridine-3-carboxylic acid analogues was carried out using chlorpheniramine as the standard drug. Ligand dockings using Auto Dock Vina elucidated the crucial interactions in the binding pocket of H 1 R, involving residues D 3.32 , Y 3.33 , S 3.36 and Y 6.51 , for the ligands possessing satisfactory ADME profiles [ 108 ].…”

Section: Hr-targeted Ligands and Receptor Binding Site Of Inactivementioning

confidence: 99%

Molecular Modeling of Histamine Receptors—Recent Advances in Drug Discovery

Mehta

Filipek

2021

Molecules

View full text Add to dashboard Cite

The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.

show abstract

Design,in silicostudies, and synthesis of new 1,8-naphthyridine-3-carboxylic acid analogues and evaluation of their H1R antagonism effects

Abstract: New 1,8-naphthyridine-3-carboxylic acid derivatives were designed, synthesized and evaluated for their in vivo antihistaminic activity on guinea pig trachea by using chlorpheniramine maleate as the standard drug.

Cited by 21 publications

References 46 publications

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

Design, synthesis, and anti-bacterial activities of piperazine based phthalimide derivatives against superbug-Methicillin-Resistant Staphylococcus aureus

Molecular Modeling of Histamine Receptors—Recent Advances in Drug Discovery

Contact Info

Product

Resources

About