Amide Derivatives Research Articles

Synthesis of N‐Acyl Indole‐3‐Carboxaldehyde Derivatives and Polyvinyl Alcohol Acetalization with 1‐Propionylindole‐3‐Carboxaldehyde

AbstractA series of seven stable amide derivatives based on indole‐3‐carboxaldehyde were synthesized with high yields using various aliphatic and aromatic acyl chlorides, triethylamine and DMAP as the catalyst at room temperature. Structural characterization was performed using FT‐IR, 1 H‐NMR, 13C‐NMR and LC–MS techniques. To develop bioactive material, acetalization of water‐soluble polyvinyl alcohol was achieved by reacting one of the N‐acyl derivatives, 1‐propionylindole‐3‐carboxaldehyde, in the presence of a p‐TSA catalyst to form polyvinyl acetal with pendant bioactive groups. The polymer was analyzed using 1 H‐NMR, FT‐IR, TGA, DSC, FE‐SEM and EDX spectroscopic techniques. The polymer was water‐insoluble with enhanced thermal stability compared to pure polyvinyl alcohol. This approach for developing N‐acyl derivatives of indole‐3‐carboxaldehyde and then reacting one of the monomers with polyvinyl alcohol to improve its thermal properties and stability in humid conditions has proven successful.

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: <i>In Vitro</i> α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti-cardiac fibrosis activity.

Three series of N-{[4-([1,2,4]triazolo[1,5-α]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl}acetamides (14a-d, 15a-n, and 16a-f) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC50) for phosphorylation of ALK5 of 16f (9.1 nM), the most potent compound, was 2.7 times that of the clinical candidate EW-7197 (vactosertib) and 14 times that of the clinical candidate LY-2157299. The selectivity index of 16f against p38α mitogen-activated protein kinase was >109, which was much higher than that of positive controls (EW-7197: >41, and LY-2157299: 4). Furthermore, a molecular docking study provided the interaction modes between the target compounds and ALK5. Compounds 14c, 14d, and 16f effectively inhibited the protein expression of α-smooth muscle actin (α-SMA), collagen I, and tissue inhibitor of metalloproteinase 1 (TIMP-1)/matrix metalloproteinase 13 (MMP-13) in transforming growth factor-β-induced human umbilical vein endothelial cells. Compounds 14c and 16f showed especially high activity at low concentrations, which suggests that these compounds could inhibit myocardial cell fibrosis. Compounds 14c, 14d, and 16f are potential preclinical candidates for the treatment of cardiac fibrosis.

Synthesis, antifungal activity and action mechanism of novel citral amide derivatives against Rhizoctonia solani.

Rice sheath blight caused by Rhizoctonia solani is a severe threat to the yield and quality of rice. Due to the unscientific abuse of common fungicides causing resistance and environmental issues, the development of new fungicides is necessary. In this study, we used citral as the lead compound, designed and synthesized a series of novel citral amide derivatives, and evaluated their antifungal activity and mode of action against R. solani. Bioassay results indicated that antifungal activities of most citral amide derivatives against R. solani were significantly improved compared to citral, with EC50 values ranging from 9.50-27.12 mg/L. Among them, compound d21 containing the N-(Pyridin-4-yl)carboxamide group exhibited in vitro and in vivo fungicidal activities, with curative effects at 500 mg/L as effectively as the commercial fungicide validamycin·bacillus. Furthermore, d21 prolonged lag phase of the growth curve of R. solani, reduced the amount of growth, and inhibited sclerotium germination and formation. Mechanistically, d21 deformed the mycelia, increased cell membrane permeability, and inhibited the activities of antioxidant and TCA-related enzymes. Metabolome analysis showed the abundance of some energy-related metabolites within R. solani increased, and simultaneously the antifungal substances secreted by itself reduced. Transcriptome analysis showed that most genes encoding ABC transporters and peroxisomes upregulated after the treatment of d21, and cell membrane destruction. This study indicates that novel citral amide derivatives possess antifungal activity against R. solani and are expected to develop an alternative option for chemical control of rice sheath blight. This article is protected by copyright. All rights reserved.

NMI-SO2Cl2-Mediated Amide Bond Formation: Facile Synthesis of Some Dihydrotriazolopyrimidine Amide Derivatives as Potential Anti-Inflammatory and Anti-Tubercular Agents

Facile access to some novel biologically relevant dihydrotriazolopyrimidine carboxylic acid-derived amide analogues using NMI/SO2Cl2, and aromatic and aliphatic primary and secondary amines, is reported herein. The role of N-methylimidazole (NMI) as the base and sulfuryl chloride (SO2Cl2) as the coupling reagent has been effectively realized in accessing these molecules in good to excellent yields. The feasibility of the developed protocol has also been extended to the gram-scale synthesis of N-benzylbenzamide in a 75% yield from benzoic acid and benzyl amine. The newly synthesized compounds were tested via in vitro anti-inflammatory and anti-tubercular activity studies. The compounds 6aa and 6be were found to be the most active anti-inflammatory agents, whereas 6cb and 6ch were found to exhibit promising anti-tubercular potency when compared to other synthesized molecules. The structure–activity relationship (SAR) studies revealed the importance of the presence of electron-donating functionalities in enhancing the anti-inflammatory potential of the newly synthesized molecules. However, the presence of electron-withdrawing substituents was found to be significant for improving their anti-tubercular potency.

Iron‐Based Deep Eutectic Solvents: Key Players for Amide and Sulfonamide Synthesis and Alcohol Oxidation

A sustainable protocol has been devised for the oxidation of activated secondary alcohols to their corresponding carbonyl compounds, as well as their utilization as selective mono‐alkylating reagents for both amide and arylsulfonamide derivatives. These reactions proceed smoothly and in good yields (up to 98%) when conducted in Fe‐based deep eutectic solvents (DESs), which serve dual roles as solvents and catalysts. Operating under mild (40 °C) and aerobic conditions, these transformations are completed within a 4 h time frame. A pharmacologically relevant amide derivative, specifically a PMRT1 inhibitor, has also been successfully synthesized on a 3 g‐scale utilizing a reusable FeCl3·6H2O/glycerol Lewis acidic DES.

Synthesis, characterization, and biological evaluation of novel cinnamic acid derivatives: cinnamoyl-metronidazole ester and cinnamoyl-memantine amide

In this study, two derivatives, namely the ester derivative cinnamoyl metronidazole and the amide derivative cinnamoyl memantine, were synthesized from cinnamic acid and respective drugs for the purpose of exploring their potential as novel and efficient antimicrobial agents in the quest of prevailing the global antimicrobial resistance challenge.The synthesis process involved two steps: first, the chlorination of cinnamic acid using thionyl chloride, and second, the esterification of metronidazole or the amidation of memantine. These steps resulted in the formation of cinnamoyl metronidazole/memantine. Optimal reaction conditions were established, and chromatographic techniques were used to separate the synthesized compounds. Confirmation of successful synthesis was achieved through FT-IR analysis, which readily distinguished the chlorinated product and derivatives based on distinctive bands, including mainly the one of carbonyl group. Additionally, molecular structures were validated using 1H NMR and 13C NMR, with all peaks further confirming the successful esterification/amidation of cinnamoyl and drug moieties.Upon evaluating the biological activity, the parent compounds exhibited negligible effects within the tested concentration range. However, the derivatives demonstrated significant activity. The ester derivative exhibited potent activity against the Gram-positive bacterium Staphylococcus aureus, as evidenced by a zone of inhibition measuring 12–15 mm in diameter. Conversely, the amide derivative displayed appreciable biological activity against Candida fungi, with an inhibition zone measuring 11–14 mm.

Synthesis, Pharmacokinetic Profile, Anticancer Activity and Toxicity of the New Amides of Betulonic Acid-In Silico and In Vitro Study.

Betulonic acid (B(O)A) is a pentacyclic lupane-type triterpenoid that widely exists in plants. There are scientific reports indicating anticancer activity of B(O)A, as well as the amides and esters of this triterpenoid. In the first step of the study, the synthesis of novel amide derivatives of B(O)A containing an acetylenic moiety was developed. Subsequently, the medium-soluble compounds (EB171 and EB173) and the parent compound, i.e., B(O)A, were investigated for potential cytotoxic activity against breast cancer (MCF-7 and MDA-MB-231) and melanoma (C32, COLO 829 and A375) cell lines, as well as normal human fibroblasts. Screening analysis using the WST-1 test was applied. Moreover, the lipophilicity and ADME parameters of the obtained derivatives were determined using experimental and in silico methods. The toxicity assay using zebrafish embryos and larvae was also performed. The study showed that the compound EB171 exhibited a significant cytotoxic effect on cancer cell lines: MCF-7, A-375 and COLO 829, while it did not affect the survival of normal cells. Moreover, studies on embryos and larvae showed no toxicity of EB171 in an animal model. Compared to EB171, the compound EB173 had a weaker effect on all tested cancer cell lines and produced less desirable effects against normal cells. The results of the WST-1 assay obtained for B(O)A revealed its strong cytotoxic activity on the examined cancer cell lines, but also on normal cells. In conclusion, this article describes new derivatives of betulonic acid-from synthesis to biological properties. The results allowed to indicate a promising direction for the functionalization of B(O)A to obtain derivatives with selective anticancer activity and low toxicity.

In silico study of androgen receptor N-terminal domain and exploration of its modulators

The androgen receptor (AR, Uniprot: P10275) signaling plays a key role in the progression of prostate cancer, various AR-related ligands have been reported to treat prostate cancer. However, some resistance mechanisms limited the treating effect of these ligands. Since DBD binding or the allosteric binding sites in LBD of AR may allow the circumvention of some drug resistance mechanisms, anti-resistance is expected especially through the NTD (N-terminal domain) targeting. What’s more, studies have shown that compounds including EPI-001 and its derivatives which bind to the Tau-5 region on NTD could be promising molecules for AR-based therapeutics. Herein, we employed aMD (accelerated molecular dynamics) simulation to fold Tau-5 unit proteins into native structure correctly. Subsequently, based on the predicted structural features of Tau-5, the virtual screening was conducted to discover new compounds targeting AR-NTD. We picked up 8 compounds (according to their docking scores and partly similar structural consists as known AR ligands) and analyzed their interaction with Tau-5, compared with the positive control EPI-001, four of the pick-up compounds showed better glide scores. Interestingly, although compound 8 had a lower docking score, it consisted of a similar component as the ligand EIQPN and the amide derivatives, this predicts that compound 8 has also the potential to be modified into an excellent AR-NTD binding molecule. These 8 compounds were all commercially available and could be tested to check whether there was a hit compound to bind the AR-NTD and to regulate its bio-activities. Together, this study described an in silico VLS approach to discover AR-NTD ligands and provided more choices for developing AR-targeted therapies. Communicated by Ramaswamy H. Sarma

Study on the pyrolysis characteristics, kinetics, thermodynamics, volatile products, and chemical reactions of micron polyamide waste, a typical marine plastic microfragment

AbstractThe pollution of waste plastic microfragments to the marine ecosystems is an increasingly serious problem. Pyrolysis is widely recognized as a viable technique for the treatment of such plastic waste materials. The pyrolysis behaviors, characteristic parameters, kinetics, thermodynamics, volatiles, and possible chemical reactions during the pyrolysis of micron polyamide waste (the main component of fishing gear abandoned in the marine environment) are studied in inert atmosphere in the present work. The results show that the pyrolysis of micron polyamide may be regarded as a one‐step reaction. The peak and average reaction rates decrease significantly when the heating rate increases. The calculated kinetic parameters can effectively predict the pyrolysis behaviors of micron polyamide. The pyrolysis of micron polyamide is characterized as an endothermic reaction that occurs non‐spontaneously. Furthermore, the information of volatiles was obtained. The volatiles with higher content were –CH2 groups, CO2, and lactam, and the volatiles with smaller content were: –NH groups, NH3, HCN, H2O, CO, and amide derivatives. In addition, an analysis was conducted to explore the potential chemical reactions.Highlights The pyrolysis of micron polyamide can be considered as a one‐step reaction. The obtained kinetic parameters can well predict the pyrolysis process. Pyrolysis of micron polyamide is a non‐spontaneous and endothermic reaction. Specific volatile products are determined by Fourier transform infrared and mass spectrometry. The chemical reactions that may occur during the pyrolysis have been inferred.

Discovery of novel amide derivatives as potent quorum sensing inhibitors of Pseudomonas aeruginosa

With the increasing reports of antibiotic resistance in this species, Pseudomonas aeruginosa is a common human pathogen with important implications for public health. Bacterial quorum sensing (QS) systems are potentially broad and versatile targets for developing new antimicrobial compounds. While previous reports have demonstrated that certain amide compounds can inhibit bacterial growth, there are few reports on the specific inhibitory effects of these compounds on bacterial quorum sensing systems. In this study, thirty-one amide derivatives were synthesized. The results of the biological activity assessment indicated that A9 and B6 could significantly inhibit the expression of lasB, rhlA, and pqsA, effectively reducing several virulence factors regulated by the QS systems of PAO1. Additionally, compound A9 attenuated the pathogenicity of PAO1 to Galleria mellonella larvae. Meanwhile, RT-qPCR, SPR, and molecular docking studies were conducted to explore the mechanism of these compounds, which suggests that compound A9 inhibited the QS systems by binding with LasR and PqsR, especially PqsR. In conclusion, amide derivatives A9 and B6 exhibit promising potential for further development as novel QS inhibitors in P. aeruginosa.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 μM (P<0.01) and 40 μM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 μM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

Halimane Derivatives from Plectranthus ornatus Codd. as Novel Anti-cancer Agents

The Plectranthus genus is often cited for its medicinal properties. Plectranthus ornatus Codd. is traditionally used in Africa for the treatment of gastric and liver diseases and their leaves are used for their antibiotic action. The main constituent of P. ornatus is the halimane compound, 11 R∗−acetoxyhalima−5,13E−dien−15−oic acid (Hal), described for its antimicrobial and anticancer properties. The objective of this work was to improve the activity of the halimane lead molecule. Further physiochemical characterisation was performed on Hal. To the best of our knowledge, this work constitutes the first published data of the absolute configurations by SCXRD and thermal stability of Hal. Using Hal, reactions with different amines were carried out to afford novel semi-synthetic derivatives and their structural elucidation was completed. The cytotoxicity of the derivatives was assessed against three leukaemia cancer cell lines (CCRF-CEM, K562 and HL-60). The antioxidant activity was investigated using H2O2-induced HGF-1 cells and their anti-inflammatory activity was studied using RT-PCR and ELISA. Our data showed that amide derivatives of Hal presented moderate cytotoxicity and more potent activity when compared to the parent molecule, giving insight into the SAR of Hal. The derivatives also displayed protection against oxidative damage to DNA. Finally, the derivatives possessed anti-inflammatory properties at the level of gene and protein expression for the cytokines IL-1β, TNF-α and IL-6, induced by LPS in normal HGF-1 cells. Overall, our study provides useful insight into the enhanced biological activities of semi-synthetic Hal derivatives, as a starting point for novel drug formulations in cancer therapy.

Plant-Derived Caffeic Acid and Its Derivatives: An Overview of Their NMR Data and Biosynthetic Pathways.

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.

Design, synthesis, in-silico studies and apoptotic activity of novel amide enriched 2-(1H)- quinazolinone derivatives

Cancer is a broad classification of diseases that can affect any organ or body tissue due to aberrant cellular proliferation for unknown reasons. Many present chemotherapeutic drugs are highly toxic and have little selectivity. Additionally, they lead to the development of medication resistance. Therefore, developing tailored chemotherapeutic drugs with minimal side effects and good selectivity is crucial for cancer treatment. 2-(1H)-Quinazolinone is one of the vital scaffold and anticancer activity is one of the prominent biological activities of this class. Here we report the novel set of amide-enriched 2-(1H)-quinazolinone derivatives (7a-j) and their apoptotic activity with the help of MTT assay method against four human cancer cell lines: PC3 (prostate cancer), DU-145 (prostate cancer), A549 (lung cancer), and MCF7 (breast cancer). When compared to etoposide, every synthetic test compound (7a-j) exhibited moderate to excellent activity. The IC50 values of the new amide derivatives (7a-j) varied from 0.07 ± 0.0061 μM to 10.8 ± 0.69 μM. While the positive control, etoposide, exhibited 1.97 ± 0.45 μM to 3.08 ± 0.135 μM range. Among the novel amide derivatives (7a-j), in particular, 7i and 7j showed strong apoptotic activity against MCF7; 7h showed against PC3, and 7g showed against DU-145. Molecular docking studies of test compounds (7a-j) with the EGFR tyrosine kinase domain (PDB ID: 1M17) protein provided the significant docking scores for each test compound (7a-j) (−9.00 to −9.67 kcal/mol). Additionally, DFT investigations and MD simulations validated the predictions of molecular docking. According to the findings of the ADME analysis, oral absorption by humans is anticipated to be higher than 85 % for all test compounds.

Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism

BackgroundThe incidence of neuropathic pain (NP) is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate NP and the underlying mechanisms. PurposeThe present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. MethodsThe analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. ResultsOur findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 μM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. ConclusionIn summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Complexation of Hexavalent Neptunium(VI) with Oxydiacetic Acid and Its Amide Derivatives in Aqueous Solution: Spectrophotometry and DFT Calculations.

Unfolding the solution coordination chemistry of high-valent transuranium elements with the "CHON"-type ligands is important to understand the fundamental chemistry of actinides and to design more efficient extractants for partitioning of transuranium elements in advanced nuclear fuel cycles. Here, the complexation of a hexavalent neptunyl ion (NpO22+ or Np(VI)) with oxydiacetic acid (ODA) has been systematically investigated in comparison with its amide analogues N,N-dimethyl-3-oxa-glutaramic acid (DMOGA) and N,N,N',N'-tetramethyl-3-oxa-glutaramide (TMOGA) both experimentally and computationally. The formation of both 1:1 and 1:2 complexes between Np(VI) and the three ligands was identified by spectrophotometry, and their stability constants were obtained and compared with those of hexavalent U(VI) and Pu(VI). The corresponding bonding nature is elucidated by using energy decomposition analysis (EDA), electrostatic potential (ESP), ELF contours, and natural orbitals for chemical valence (NOCV) methods, which shows that the Np-O bonds are essentially ionic in character and the unoccupied 6d orbitals of Np play a key role in enhancing the covalent interactions between Np(VI) and the three ligands.

Synthesis of Amides and Salts of Oxalic Acid and Their Use as Plant Growth Regulators

Oxalic acid plays a very important role in the life of plant organisms. In addition, its salts and amide derivatives also have growth-stimulating properties. In this work, we show the results of research in the field of synthesis of amide derivatives of oxalic acid, and also investigated their growth properties using the example of some agricultural crops. Have found that the mono amide of oxalic acid has a stronger effect on the growth of pea seeds compared to the disubstituted amide of this acid. Thus, we can conclude that salts and amide derivatives of oxalic acid have a pronounced regulatory property during the ripening of pea and corn seeds. In this regard, they have been recommended as growth stimulants for these plants in agricultural practice.

A Combination of Pharmacophore Generation, Ligand-based Virtual Screening, Atom-based 3D-QSAR, and Molecular Docking Studies on Febuxostat-based Amides Analogues as Anti-inflammatory Agents.

A defence mechanism of the body includes inflammation. It is a process through which the immune system identifies, rejects, and starts to repair foreign and damaging stimuli. In the world, chronic inflammatory disorders are the leading cause of death. To obtain optimized pharmacophore, previously reported febuxostat- based anti-inflammatory amide derivatives series were subjected to pharmacophore hypothesis, ligand-based virtual screening, and 3D-QSAR studies in the present work using Schrodinger suite 2022-4. QuikProp module of Schrodinger was used for ADMET prediction, and HTVS, SP, and XP protocols of GLIDE modules were used for molecular docking on target protein (PDB ID:3LN1). Utilising 29 compounds, a five-point model of common pharmacophore hypotheses was created, having pIC50 ranging between 5.34 and 4.871. The top pharmacophore hypothesis AHHRR_ 1 model consists of one hydrogen bond acceptor, two hydrophobic groups and two ring substitution features. The hypothesis model AHHRR_1 underwent ligand-based virtual screening using the molecules from Asinex. Additionally, a 3D-QSAR study based on individual atoms was performed to assess their contributions to model development. The top QSAR model was chosen based on the values of R2 (0.9531) and Q2 (0.9424). Finally, four potential hits were obtained by molecular docking based on virtual screening. The virtual screen compounds have shown similar docking interaction with amino acid residues as shown by standard diclofenac sodium drugs. Therefore, the findings in the present study can be explored in the development of potent anti-inflammatory agents.

High anti Diastereoselectivity in a Tandem Oxyhomologation-Coupling Protocol for the Preparation of Amides and Peptides Incorporating α-Hydroxy β-Amino Acids.

The one-pot MAC (Masked Acyl Cyanide) reaction is used to perform the tandem oxyhomologation reaction of N,N-dibenzyl-l-phenylalaninal and coupling with nitrogen nucleophiles to provide a wide selection of amide and peptide derivatives of (2S,3S)-allophenylnorstatin in generally good yields and with high anti selectivity, often with dr >98:2. The procedure works equally well with other selected N,N-dibenzyl α-amino aldehydes, and is used to achieve a very short synthesis of (2S,3S,S)-epibestatin.