Pyrimidine Derivatives Research Articles

A Review on Facile Synthesis of Pyrimidine Derivatives via Multicomponent Reactions

A Review on Facile Synthesis of Pyrimidine Derivatives via Multicomponent Reactions

Synthesis, spectral study and evaluation of antibacterial activity of some novel 4-(6-methoxynaphthalen-2-yl)-6-(substituted aryl)pyrimidine-2(1H)-thiones

Abstract The objective of this study was to synthesize some novel substituted 4-(2-methoxynaphthalen-6-yl) pyrimidine- 2(1H)-thione compounds using sodium hydroxide catalyzed three component condensation and cyclization reaction of substituted 6-methoxy-2-acetonapthone, various substituted benzaldehydes and thiourea. These thione derivatives were characterized by their analytical, physical, and spectroscopic data. In addition, the in vitro antibacterial activities of these pyrimidine derivatives were evaluated using Bauer-Kirby disc diffusion method.

In Silico Exploration of few TriazoloPyrimidine Derivatives as Virtual Inhibitors against SARS-CoV-2 : A Comprehensive Analysis Integrating Molecular Docking and ADME-Toxicity Evaluation

This ground-breaking research delves into the potential of novel triazolopyrimidine derivatives as inhibitors of SARS-CoV, employing a robust in-silico approach that integrates molecular docking studies, molecular dynamics simulations, and comprehensive ADMET parameter assessments. The overarching goal is to identify compounds that exhibit both robust binding affinity and favourable pharmacokinetic profiles, laying the foundation for potential antiviral drug development. The methodology begins with the meticulous selection of triazolo pyrimidine derivatives based on their structural characteristics. Molecular docking studies are then conducted, focusing on a specific binding site on the SARS-CoV target. Subsequent molecular dynamics simulations provide a dynamic perspective on the stability of the binding interactions over time. ADMET parameter assessments are employed to evaluate drug-likeness and safety, crucial factors in determining the compounds' viability as potential drug candidates. The findings of this research underscore promising interactions between the triazolo pyrimidine derivatives and the targeted viral site, suggesting their potential as inhibitors of SARS-CoV. Importantly, the ADMET assessments contribute valuable insights into the pharmacokinetic properties of the compounds, informing their overall safety and suitability for further development. Notably, molecular docking studies include a comparative analysis with the standard antiviral drug remdesivir, revealing that the triazolo pyrimidine derivatives exhibit energy scores surpassing those of remdesivir. This finding signifies a potential advantage in terms of binding affinity and effectiveness against SARS-CoV. The implications of this research are profound, extending beyond the identification of potential inhibitors for SARS-CoV to contributing essential knowledge for the development of therapeutics against coronaviruses in general. This study serves as a crucial stepping stone for subsequent experimental validation and optimization of the identified compounds, propelling future drug discovery endeavours in the fight against coronaviral infections.

Robust leishmanicidal upshot of some new diphenyl triazine-based molecules.

Amongst the neglected tropical diseases, leishmaniasis alone causes 30 000 deaths annually due to the protozoan parasite genus Leishmania. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost. Therefore, new safer and shorter treatments are an urgent need of the time. Herein, we report the synthesis of fifteen novel diphenyl triazine and diphenyl triazine pyrimidine derivatives and their antileishmanial properties against Leishmania donovani, that causes fatal visceral leishmaniasis. Most of the synthesized analogues exhibited more than 90% inhibition against the promastigote stage of the parasite. Moreover, compounds T4 and T7 showed potent activity against extracellular promastigote (IC50 = 1.074 μM and IC50 = 1.158 μM) as compared to miltefosine (IC50 = 1.477 μM) and is nontoxic towards the host THP-1 macrophage cell line. Interestingly, compound T4 exhibited significant activity against amastigotes (7.186 μM) and induced the macrophages to prevent the survival of the parasite. Our results indicate that T4 represents a new structural lead for this serious and neglected disease.

Design, synthesis and antitumor activity of 4-arylamine substituted pyrimidine derivatives as noncovalent EGFR inhibitors overcoming C797S mutation

Clinical researches have shown that epidermal growth factor receptor (EGFR) is a key target for treatment of non-small cell lung cancer (NSCLC). Many EGFR inhibitors were successfully developed as ani-tumor drugs to treat NSCLC patients. Unfortunately, drug resistances were found in clinic. To overcome C797S mutation in EGFR, a novel series of 4-arylamine substituted pyrimidine derivatives were designed and synthesized under the principle of structure-based drug design. Interestingly, compounds 6e and 9i demonstrated the best anti-proliferative activity against A549, NCI–H1975, and HCC827 cells. In particular, the IC50 values against HCC827 cells reached to 24.6 nM and 31.6 nM, which were much lower than human normal cells 2BS and LO2. Furthermore, compounds 6e and 9i showed extraordinary activity against EGFR19del/T790M/C797S (IC50 = 16.06 nM and 37.95 nM) and EGFRL858R/T790M/C797S (IC50 = 11.81 nM and 26.68 nM), which were potent than Osimertinib (IC50 = 52.28 nM and 157.60 nM). Further studies have shown that compounds 6e and 9i could pertain inhibition of HCC827 colony formation, and arrest HCC827 cells at G2/M phase. Moreover, the most promising compound 6e could inhibit the migration of HCC827 cells, induce HCC827 cells apoptosis, and significantly inhibit the phosphorylation of EGFR, AKT and Erk1/2. In vivo xenograft mouse model with HCC827 cells, compound 6e resulted in remarkable tumor regression without obvious toxicity. In addition, molecular docking studies suggested that compound 6e could firmly combine with T790M-mutant, T790 M/C797S-mutant, and L858R/T790 M/C797S-mutant EGFR kinases as ATP-competitive inhibitor.

FeCl3‐Catalyzed C(sp3)−H Heteroarylation Enabled by Photoinduced Ligand‐to‐Metal Charge Transfer

AbstractHerein, we report a strategy for pyrimidination of inert alkanes via synergistic visible light‐driven redox reaction and FeCl3 catalysis. This transformation involves C−H activation by a chlorine radical generated during the iron‐promoted ligand‐to‐metal charge transfer process, triggering subsequent C−H pyrimidination. The substrates and catalysts are inexpensive and readily available, while the reaction conditions and procedures are simple without the need for external oxidants. This work provides a practical approach for synthesizing pyrimidine derivatives with high structural diversity.

Discovery of Novel Compounds for Combating Rising Severity of Plant Diseases Caused by Fungi and Viruses.

In recent years, the severity of plant diseases caused by plant pathogenic fungi and viruses has been on the rise. However, there is a limited availability of pesticide chemicals in the market for effectively controlling both fungal and viral infections. To solve this problem, a series of novel pyrimidine derivatives containing a 1,3,4-oxadiazole thioether fragment were synthesized. Among them, compound 6s exhibited remarkable in vivo protection activity against tobacco mosaic virus, demonstrating the superior 50% effective concentration (EC50) value of 0.42 μM, outperforming ningnanmycin (0.60 μM). Meanwhile, compound 6s exhibited remarkable antifungal activity against Botrytis cinerea Pers. in postharvest blueberry in vitro, with an EC50 value of 0.011 μM, surpassing the inhibition rate of Pyrimethanil (0.262 μM). Additionally, compound 6s also demonstrated remarkable curative and protection activities against blueberry fruit gray mold in vivo, with control efficiencies of 54.2 and 60.4% at 200 μg/mL concentration, respectively, which were comparable to those of Pyrimethanil (49.3 and 63.9%, respectively). Scanning electron microscopy showed that the compound 6s-treated hyphae of B. cinerea Pers. in postharvest blueberry became abnormally collapsed and shriveled. Furthermore, the molecular docking simulation demonstrated that compound 6s formed hydrogen bonds with SER-17, ARG-43, and SER-39 of succinate dehydrogenase (SDH), providing a possible explanation for the mechanism of action between the target compounds and SDH. This study represents the first report on the antiviral and antifungal activities of novel pyrimidine derivatives containing a 1,3,4-oxadiazole thioether fragment.

Determination of the Anti-Escherichial Activity of the Pyrimidine Derivative 3-[2-[(4,6-dimethylpyrimidin-2- yl)amino]-2-oxoethyl]quinazolin-4(3H)-one

The aim of this study was to investigate the antimicrobial activity of the pyrimidine derivative 3-[2-[(4,6-dimethylpyrimidin-2-yl)amino]-2-oxoethyl]quinazolin-4(3H)-one against Escherichia coli. The study of antimicrobial activity was carried out in vitro by serial dilutions of the pyrimidine compound, followed by determination of the minimum inhibitory concentration of 3-[2-[(4,6-dimethylpyrimidin-2-yl)amino]-2-oxoethyl]quinazolin-4(3n)-one (VMA-13-14) and in vivo on the model of generalized E.coli infection. The study of antimicrobial activity in vivo was carried out on 40 CBA mice weighing 19–20 g. All manipulations with animals were performed in accordance with the requirements of the regulatory documentation governing the maintenance of laboratory animals and work involving them. The antimicrobial activity of the pyrimidine compound 3-[2-[(4,6-dimethylpyrimidin-2-yl)amino]-2-oxoethyl]quinazolin-4(3H)-one against E.coli in vitro was evaluated in terms of mouse survival, contamination of blood and internal organs (liver, spleen, lungs, brain), as well as the total number of leukocytes and leukograms. The experiment determined that the pyrimidine compound 3-[2-[(4,6-di- methylpyrimidin-2-yl)amino]-2-oxoethyl]quinazolin-4(3n)-one demonstrates antimicrobial activity against E.coli: in vitro, it has a bactericidal effect at a concentration of 128 µg/ml; in vivo, it has an antimicrobial effect in conditions of generalized infection with the introduction of 50 mg/kg/day for 10 days. The antimicrobial effect of 3-[2-[(4,6-dimethylpyrimidin-2- yl)amino]-2-oxoethyl]quinazolin-4(3n)-one is comparable to ceftazidime, which is the drug of choice in the treatment of E.coli infection.

Rational synthesis and evaluation of 2,4-diamino-thieno[2,3-d]pyrimidines as antitumor agents

Based on structure-guided of thieno[2,3-d]pyrimidine skelecton functionalities and computer-aided drug development strategy, a series of novel 2,4-diamino-thieno[2,3-d]pyrimidine derivatives were designed and synthesized, and their structure confirmed by 1H NMR, 13C NMR and HR-MS. All synthesized compounds were evaluated for antitumor activities against hepatic carcinoma (HepG2) cell lines in vitro, and results showed that all the target compounds exhibited potent antitumor activity. Preliminary comparison indicated that a more bulky substituent group at the C-4 position, and at the same time the introduction of 3-Cl on the phenyl ring with 4-methyl group on the C-2 position of thieno[2,3-d]pyrimidine have remarkable influence on activity. One of the expected target compound 5i showed the best inhibition activities against HepG2 with IC50 value 0.17 μmol/L. To further investigate the structure-activity relationship, the docking experiment of 5i, 5j, 5o and Gefitinib on EGFR were performed. The docking results displayed that compound 5i was able to be tightly embedded in the active pocket of EGFR and the binding energy is most negative with EGFR, which demonstrating that compound 5i can be take a potential lead compound for further lucubrate.

Synthesis of Benzoate‐Based Functionalized Ionic Liquids: Relationship between Supramolecular aggregation behavior and Catalytic activity in Phenyl Pyrimidines Derivatives

AbstractThis study reports synthesizing and characterizing imidazolium‐based ionic liquids (ILs) using substituted benzoates as anions. Thermal stability of ILs described using thermogravimetric analysis (TGA). One inherent property of ILs is aggregates or cluster formation due to supramolecular interactions. The supramolecular interaction in synthesized ILs has been studied through Electrospray ionization mass spectrometry (ESI‐MS). The potential of ILs as organic catalysts is investigated in multicomponent reaction (MCR) using urea, malononitrile, and different aromatic aldehydes to prepare phenyl pyrimidines derivatives. The results demonstrate that catalysis with ILs effectively reduces reaction time and enhances yield. ILs entities are hypothesized to form new assemblies with reactive moieties of reactants through supramolecular interactions. The ILs can be reused and recycled.

Traditional, one-pot three-component synthesis and anti-bacterial evaluations of some new pyrimidine derivatives

In this study, a novel series of pyrimidine compounds featuring azo linkages was synthesized via a sequence of stepwise and one-pot three-component reactions. The synthetic process commenced with the diazotization of 3-chloro-4-methyl aniline, followed bycoupling reaction with 4-hydroxy acetophenone, yielding the azo molecule denoted as 1-(3-((3-chloro-4-methylphenyl)diazenyl)-4-hydroxyphenyl)ethan-1-one. Subsequently, this compound underwent benzylation with benzyl bromide by Williamson ether synthesis, leading to the formation of 1-(4-(benzyloxy)-3-((3-chloro-4-methylphenyl)diazenyl)phenyl)ethan-1-one. The resultant azo-benzyloxy compound was then subjected to both classical and one-pot methodologies to synthesize pyrimidine derivatives, from results obtained from one pot reaction were in good yield. Structural elucidation of the newly synthesized compounds was characterized by spectral analysis, including FT-IR, 1H NMR, 13C NMR, and 13C-DEPT-135-NMR. The spectroscopic data confirmed the integrity of the molecular structures. Lastly, certain pyrimidine derivatives were evaluated for their antimicrobial activity against two strains of bacteria, namely Staphylococcus aureus and Escherichia coli. The results revealed that as the increasing of concentration, the sensitivity increased as reached 800 µg /mL no growth of bacterial was seen, It is also notable that the synthesized compounds have antimicrobial efficacy against both bacterial types.

BF3@K10: An Efficient Heterogeneous Montmorillonite Catalyst for the Halogenation of N-Heterocycles

AbstractHalogenated N-heterocycles are an essential structural building block in medicinal chemistry. Herein, we describe an economical and efficient protocol for the regioselective halogenation of several N-heterocycles (pyrimidines, a pyrazole, 2-aminopyridine, theophylline, and an imidazo[1,2-a]pyridine) with BF3-doped montmorillonite (BF3@K10). The new catalyst was characterized by FTIR and 11B NMR spectroscopy, XRD, SEM, and EDS. The developed strategy provides easy and fast access to iodo-, bromo-, and chloro-N-heterocycles under mild conditions. This method was used to synthesize nine new halogenated pyrimidine derivatives. The reaction is simple and general, affording good to excellent yields of products under conventional heating or microwave conditions in the presence of BF3@K10 as an ecofriendly, inexpensive, and efficient catalyst. This protocol is clearly superior to the conventional route because it offers short reaction times, high yields, and easy workup.

Diversification Via Coupling Reactions and Biological Activities of Pyrimidine Derivatives

AbstractPyrimidine derivatives have attracted much attention in medicinal chemistry because of their diversified biological properties and potential therapeutic applications. The Suzuki‐Miyaura, Sonogashira, and Buchwald‐Hartwig coupling reactions provide flexible methods for synthesizing structurally diverse pyrimidine derivatives. These reactions can modify the pyrimidine structure to incorporate different functional groups and substitution patterns, improving the pharmacological activities and maximizing the drug‐like properties. Using other coupling partners, such as aryl and heteroaryl moieties, has produced novel pyrimidine‐based scaffolds with enhanced bioactivity profiles. This comprehensive review examines the biological activities of pyrimidine derivatives, concentrating on how their diversification via coupling reactions utilizing synthetic techniques has affected their pharmacological properties. Investigating various biological effects and exploring novel artificial techniques present great opportunities for creating next‐generation medicines with improved efficacy and selectivity.

Screening of Auxin-like Substances among Synthetic Compounds, Derivatives of Pyridine and Pyrimidine

The effect of known synthetic compounds Ivin (N-oxide-2,6-dimethylpyridine), Methyur (sodium salt of 6-methyl-2-mercapto-4-hydroxypyrimidine), Kamethur (potassium salt of 6-methyl-2-mercapto-4-hydroxypyrimidine) and new synthetic compounds, derivatives of pyrimidine (No. 1 - 7) on the rooting of isolated stem cuttings of haricot bean (Phaseolus vulgaris L.) variety Bilozernaya was studied. The growth regulatory activity of synthetic compounds Ivin, Methyur, Kamethur, and synthetic compounds, derivatives of pyrimidine (No. 1 - 7) was compared with the activity of auxins IAA (1H-indol-3-yl)acetic acid) and NAA (1-naphthylacetic acid). The conducted studies showed that the regulatory effect of synthetic compounds Ivin, Methyur, Kamethur, and synthetic compounds, derivatives of pyridine (No. 1 - 7) on the rooting of isolated stem cuttings of haricot bean was similar to the auxins IAA and NAA. The synthetic compounds Ivin, Methyur, and Kamethur, and synthetic compounds, derivatives of pyrimidine (No. 1, 4, 5, and 7) showed the highest auxin-like activity. The indicators of the total number of roots (pcs) and total length of roots (cm) obtained on isolated stem cuttings of haricot bean immersed in a water solution of synthetic compounds Ivin, Methyur, Kamethur and synthetic compounds, derivatives of pyridine (No. 1, 4, 5 and 7), used at a concentration of 10-7 M, statistically significantly exceeded similar indicators obtained on control isolated stem cuttings of haricot bean immersed in distilled water. The practical use of synthetic compounds Ivin, Methyur, Kamethur, and synthetic compounds, derivatives of pyrimidine (No. 1, 4, 5 and 7) is proposed to improve the vegetative propagation of haricot bean plants (Phaseolus vulgaris L.) and other plant species of the family Fabaceae by stem cuttings.

Integrated computational approaches for designing potent pyrimidine-based CDK9 inhibitors: 3D-QSAR, docking, and molecular dynamics simulations

CDK9 is an emerging target for the development of anticancer drugs. The development of CDK9 inhibitors with significant potency had consistently posed a formidable challenge. In the current research, a number of computational methodologies, such as, 3D-QSAR, molecular docking, fingerprint analysis, molecular dynamic (MD) simulations followed by MMGB/PBSA and ADMET studies were used systemically to uncover the binding mechanism of pyrimidine derivatives against CDK9. The CoMFA and CoMSIA models having high q2 (0.53, 0.54) and r2 values (0.96, 0.93) respectively indicating that model could accurately predict the bioactivities of CDK9 inhibitors. Using the R-group exploration technique implemented by the Spark™ by Cresset group, the structural requirements revealed by the contour maps of model were utilized strategically to create an in-house library of 100 new CDK9 inhibitors. Additionally, the compounds from the in-house library were mapped into 3D-QSAR model which predicted pIC50 values comparable to the experimental values. A comparison between 3D-QSAR generated contours and molecular docking conformation of ligands was performed to elucidate the essentials of CDK9 inhibitor design. MD simulations (100 ns) were performed on the selected docked complexes A21, A14 and D98 which contributed in validating the binding interactions. According to the findings of binding free energy analysis (MMGB/PBSA), It was observed that residues CYS106 and GLU107 had a considerable tendency to facilitate ligand-protein interactions via H-bond interactions. The aforementioned findings have the potential to enhance researchers comprehension of the mechanism underlying CDK9 inhibition and may be utilized in the development of innovative and efficacious CDK9 inhibitors.

New library of pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: Synthesis, herbicidal activity, and molecular docking study

The development of nitrogen-containing heterocyclic compounds with novel structure and remarkable biological activity is always in demand. Herein, new library of pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives (1–98) was designed, synthesized, and characterized by Fourier Transform Infrared Spectoscopy (FT-IR), nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), high-resolution mass spectroscopy (HRMS), and X-ray single-crystal diffraction. Their herbicidal activities were screened for the first time by Petri dish assay and pot experiment in a glasshouse. The results indicated that some of title compounds (e.g.,1, 4, 5, and 7–11) exhibited 100 % inhibition rate against the roots and stalks of Cucumis sativus, Raphanus sativus, Sorghum bicolor and Echinochloa crusgalli at a dosage of 100 mg/L, higher than the positive control Flumetsulam, a well-known commercial acetolactate synthase (ALS) inhibiting herbicide. 2-((2,4-Dichlorophenoxy)methyl)-10-(methylthio)-8-(pentylthio)-5-propyl-5,6-dihydropyri- mido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine 7 showed notable postemergence herbicidal activity against Abutilon theophrasti, Amaranthus spinosus, Chenopodium album, Digitaria sanguinalis, Echinochloa crusgalli, and Setaria viridis at a rate of 375 g/ha, and its activities were similar to the positive control Flumetsulam. Enzymatic bioassays revealed that 7, 8, and 40 displayed good inhibitory potency against ALS with 39.6 %, 39.1 %, and 40.9 % inhibition rate, respectively, comparable to that of Flumetsulam (43.5 % inhibition rate). Moreover, molecular docking analysis was conducted by using ALS protein and target ligand molecule 7. The results of molecular docking were consistent with the bioassay experiments, showing compound 7 with a new structure and excellent herbicidal potency was potent inhibitors of ALS.

Identification of potential drug molecules against fibroblast growth factor receptor 3 (FGFR3) by multi-stage computational-biophysics correlate

The fibroblast growth factor receptor 3 (FGFR3) is warranted as a promising therapeutic target in bladder cancer as it is described in 75% of papillary bladder tumors. Considering this, the present study was conducted to use different approaches of computer-aided drug discovery (CADD) to identify the best binding compounds against the active pocket of FGFR3. Compared to control pyrimidine derivative, the study identified three promising lead structures; BDC_24037121, BDC_21200852, and BDC_21206757 with binding energy value of −14.80 kcal/mol, −12.22 kcal/mol, and −11.67 kcal/mol, respectively. The control molecule binding energy score was −9.85 kcal/mol. The compounds achieved deep pocket binding and produced balanced interactions of hydrogen bonds and van der Waals. The FGFR3 enzyme residues such as Leu478, Lys508, Glu556, Asn562, Asn622, and Asp635. The molecular dynamic (MD) simulation studies additionally validated the docked conformation stability with respect to FGFR3 with a mean root mean square deviation (RMSD) value of < 3 Å. The root mean square fluctuation (RMSF) complements the complexes structural stability and the residues showed less fluctuation in the presence of compounds. The Poisson–Boltzmann or generalized Born and surface area continuum solvation (MM/PBSA and MM/GBSA) methods revalidated compounds better binding and highlighted van der Waals energy to dominate the overall net energy. The docked stability was additionally confirmed by WaterSwap and AMBER normal mode entropy energy analyses. In a nutshell, the compounds shortlisted in this study are promising in term of theoretical binding affinity for FGFR3 but experimental validation is needed.Communicated by Ramaswamy H. Sarma

Efficient energy levels and lifetimes regulation of excited states for narrowband thermally activated delayed fluorescence

Multiple resonance thermally activated delayed fluorescence (MR-TADF) materials attract much attention owing to their 100 % exciton utilization, high photoluminescence quantum yield (PLQY) and narrowband emission with high color purity. However, how to regulate the energy levels and lifetimes of excited states for long-wavelength and short delayed fluorescence lifetime MR-TADF materials is still a challenge. Herein, an electron acceptor unit of pyrimidine derivative is introduced with steric-hinerance effect. The emission spectrum of BN-DPP is red shifted with 15 nm and the full width at half maximum (FWHM) is even narrower of 20 nm compared with that of DtCZB. A yellow-green MR-TADF material, called BN-DPBQ, is fabricated by extended the conjugation. Moreover, the delayed fluorescence lifetime of BN-DPBQ is half of that of BN-DPP. The BN-DPP based devices exhibit greenish blue emission with peak locating at 494 nm and maximum external quantum efficiency (EQE) of 23.6 %. BN-DPBQ based ones show much red shifted spectrum with emission peak at 538 nm and maximum EQE of 20.3 %. The results indicate that introducing electron acceptor units with steric-hinerance effect and extending the conjugation of resonance skeleton are effective ways to regulate energy levels and lifetimes of excited states for MR-TADF.

Determination of New 4-Aryl-pyrido[1,2-c]pyrimidine Derivatives, Potential Antidepressant Agents with a High Affinity to 5-Hydroxytryptamin 1A Receptor and Serotonin Transporter Protein Receptor, with Capillary Electrophoresis

A novel capillary electrophoresis method was developed for the determination of new 4-aryl-pyrido[1,2-c]pyrimidine derivatives, potential antidepressant agents, in serum. The derivatives have conformationally restricted tryptamine moiety in pharmacophore portion and exhibit high affinity to molecular targets: 5-HT1A receptor and serotonin transporter protein. The separation process was conducted using an eCAP fused-silica capillary, detection wavelength 214 nm, 200 mM phosphate buffer adjusted to pH = 8.0, temperature 20 °C, voltage 5 kV. The proposed method was validated by determining its linearity in the concentration range of 200–1000 ng/mL. A satisfactory linearity was obtained for the method, with R2 from 0.9978 to 0.9999 for all five derivatives and a limit of quantification level from 287.1 to 310.1 ng/mL. The recoveries for all derivatives were in the range from 94.7 to 100%. The speed of obtaining the result of the analysis was only 3 min. The developed method allows to determine all five derivatives both in water solutions and serum.

Development of New 5‐(Oxazol‐2‐yl)Pyrimidine Derivatives with Promising Anticancer Activities

AbstractA novel series of oxazolyl‐pyrimidine derivatives (11 a–j) have been synthesized and structures were confirmed by spectral data. The synthesized compounds were assessed for cytotoxic profile towards human cervix cancer (SiHa), lung cancer (A549), breast cancer (MCF‐7), and colon cancer (Colo‐205) cell lines by employing MTT assay and using etoposide as the positive control. The heteroaryl compounds having the terminal pyridyl (11 a) and thiazolyl (11 b) groups showed superior cytotoxic potency against cervix and lung cancer cell lines and varying methoxy substituted derivatives 11 c–11 e have excellent to good cytotoxic properties. Compound 11 a and 11 b have IC50 values in the range of 0.01±0.0034 to 0.17±0.059 μM and 0.10±0.038 to 0.66±0.077 μM respectively in the tested cell lines. The selected compounds 11 a and 11 b were studied by molecular docking to assess the binding interactions, binding energies, and possible mechanisms. The in‐silico ADME properties were calculated and all the compounds have the desired properties of drug‐like molecules. The toxicity results indicate that all the compounds are free from toxicity except 11 j, which has high tumorigenic properties. The optimized structure, energies of frontier molecular orbitals, molecular electrostatic potential, and NLO parameters for compound 11 a were determined using DFT/B3LYP level with a 6‐311++G(d,p) basis set.