Pyrimidine Series Research Articles

New 1,3-diphenyl-1H-pyrazol-5-ols as anti-methicillin resistant Staphylococcus aureus agents: Synthesis, antimicrobial evaluation and in silico studies

In the present work, two hybrid series of pyrazole-clubbed pyrimidine and pyrazole-clubbed thiazole compounds 3–21 from 4-acetyl-1,3-diphenyl-1H-pyrazole-5(4H)-ole 1 were synthesized as novel antimicrobial agents. Their chemical structures were thoroughly elucidated in terms of spectral analyses such as IR, 1H NMR, 13C NMR and mass spectra. The compounds were in vitro evaluated for their antimicrobial efficiency against various standard pathogen strains, gram -ive bacteria (Pseudomonas aeruginosa, Klebsiella pneumonia), gram + ive bacteria (MRSA, Bacillus subtilis), and Unicellular fungi (Candida albicans) microorganisms. The ZOI results exhibited that most of the tested molecules exhibited inhibition potency from moderate to high. Where compounds 7, 8, 12, 13 and 19 represented the highest inhibition potency against most of the tested pathogenic microbes comparing with the standard drugs. In addition, the MIC results showed that the most potent molecules 7, 8, 12, 13 and 19 showed inhibition effect against most of the tested microbes at low concentration. Moreover, the docking approach of the newly synthesized compounds against DNA gyrase enzyme was performed to go deeper into their molecular mechanism of antimicrobial efficacy. Further, computational investigations to calculate the pharmacokinetics parameters of the compounds were performed. Among them 7, 8, 12, 13 and 19 are the most potent compounds revealed the highest inhibition efficacy against most of the tested pathogenic microbes comparing with the standard drugs.

Expanding the Scope of Group Transfer Radical Reaction: Toward the Synthesis of Fluorinated Nucleoside Analogues Incorporating Difluorophosphonylated Allylic Ether Moieties.

Scope and limitations of the group transfer radical reaction of diisopropyl iododifluoromethylphosphonate onto carbohydrates and nucleosides are described. This key step allowed us to explore the synthesis of new fluorinated nucleoside analogues containing a difluorophosphonylated allylic ether moiety onto the 2'-position, in purine and pyrimidine series (B = A, C, G, T, U). Indeed, two unprecedented chemical approaches involving a late introduction of either the nucleobase or the fluorinated moiety are discussed.

Study of the biological properties of new chemical compounds of the pyrimidine series

In order to study the effect of a number of 6-substituted uracil derivatives on bovine embryo lung cells, experiments were conducted. According to the study, the effect of the studied substances on the cultural and morphological properties of cell was determined by taking into account their viability and proliferation index. In %, it was calculated that viability was determined by the ratio of living cells to their total number. The proliferation index was determined as the ratio of the number of proliferating cells to the number of seeded cells. At 0.1 mM concentration of the compounds studied, a decrease in LEK cell viability was recorded compared to the control group, but this was only the case for compound No. 2. When other compounds were used at doses of 0.1 mM, LEK cell viability increased by 3.0-7.0% compared to controls. Increasing the dose of the compounds studied to 1.0 mM results in a 10.0% decrease in survival in the presence of compounds No. 3 and 6, 16.0% in the presence of compounds No. 2 and 7, 19.0% in the presence of compound No. 4 and 25.0% in the presence of compounds No. 8 and 9.

Synthesis and pharmacological evaluation of selective MAO-A inhibitors using structure and pharmacophore-based drug design

A combined pharmacophore and structure-based modeling method was used to study monoamine oxidase A interaction with known ligands. Pharmacophore and docking models have been worn to determine selective MAO-A inhibitors, and they agree well with docking data. In the ideal pharmacophore model, two hydrogen bonds acceptors, one hydrophobic aliphatic characteristic, and one aromatic ring characteristic are necessary. A selective MAO-A drug is identified using the structural novelty and selectivity index. UV, IR, 1H NMR, and mass spectral data were worn to characterize the Pyrimidine series of admixture. The "Porsolt behavioral despair test" on Swiss-albino mice was used to assess the antidepressant efficacy of these substances. It was found that the compounds were having comparable antidepressant activity to that of standard drug imipramine at 20 mg/kg body weight.

Pyrimidine Tethered Pyrazoles: Synthesis, Biological, and Molecular Docking Studies

A series of pyrimidine integrated pyrazoles (5a?5g) has been synthesized in good yields from aryl hydrazines and aralkyl ketones through a protocol of multi-steps such as condensation/imine formation, cyclization/Vilsmeier-Haackreaction, and Knoevenagelcondensation and characterized through physical and spectral techniques. 2,2-diphenylpicrylhydrazyl radical scavenging evaluation revealed that the chemical entity possessing para-fluoro substituent on the aromatic unit tethered at the carbon of pyrazole scaffold 5g exerted the highest activity among the investigated ones. Of the results of cytotoxicity evaluation utilizing AsPC1, BxPC3, SW1990 (pancreatic cancer cells), the chemical entity possessing ortho-chlorosubstitient on the aryl unit integrated at carbon of pyrazole scaffold 5b exhibited superior activity. Besides, the molecular docking studies of the ortho-chloroaryl group possessing chemical entity 5b with BCL-2 (B-cell lymphoma 2) displayed significant binding affinity (-9.1 kcal mol-1). In addition, pharmacokinetic as well as prediction of drug-likeness for all the molecular hybrids 5a?5g have been evaluated using SwissADME tool and all the chemical entities are in good agreement of Lipinski rule with no violation.. KEYWORDS :Cytotoxicity, Molecular docking, Pyrazoles, Pyrimidines, Radical scavenging, SwissADME.

Complexes of Ionized Dipeptides of Glycyl-L-Glutamic Acid and Alanyl-L-Tyrosine with Nucleic Bases of the Pyrimidine Series

Complexes of Ionized Dipeptides of Glycyl-L-Glutamic Acid and Alanyl-L-Tyrosine with Nucleic Bases of the Pyrimidine Series

Pyrimidine and cumene derivatives functionalized by hydroxy and methoxy: Computational insights in drug-likeness, ADM, and toxicity studies

The –OH and –OCH3 functionalized isopropyl cumene and isopropyl pyrimidine derivatives were designed and, explored in terms of the ADM, and possible toxic effects in view of the medicinal and environmental. For this goal, the geometry optimizations and structural confirmations were conducted by the G09W package at B3LYP/6-311G** level of theory. The verified geometries were used for further computations and analyses. The bioavailability features such as lipophilicity, water solubility, and drug-likeness, pharmacokinetics were determined by SwissADME tools. Also, ADMETLab computations were used to predict the absorption, distribution, metabolism, and toxicity of the data set. The FMO and NBO analyses were performed to determine the –OH and –OCH3 function effect on the cumene and pyridine structures and then the electronic properties underlying the bioavailability and toxicity properties. Accordingly, the –OCH3 function on the structure l seems to be important to rise the inhibitory or substrate potency in the enzyme metabolism for both series. For the pyrimidine series, the anomeric interactions (n → σ*) in addition to the resonance interactions (n → π* and π → π*) also would have a role in molecular stability and affect the charge distribution on the molecular surface, which could play of remarkable role in the bioavailability and ADM. In terms of electronic structure and physicochemical properties, and possible bioactivity or toxicity relationship, the results obtained in the study will be an important reference source for the research on exploring/developing/improving future biocompatible molecular structures.

Novel pyrimidine – Imines against tuberculosis: Rationale, in vitro, in silico studies and mechanistic insights

Two series of novel multifunctional pyrimidine–imine hybrids were synthesized and evaluated for their antitubercular and antimicrobial properties. A novel synthetic methodology utilizing water as a green solvent and a catalytic amount of HCl resulted in the isolation of barbituric acid – uracil – imine hybrids in moderate to good yields. The in vitro antitubercular activity of the compounds revealed exceptional activity, with D16 showing MIC100 at 6 µM, which is comparable to the commercial drug ethambutol with MIC100 at 7.63 µM. Compounds D7, D12, D18, D19, and D20 also showed MIC100 at concentrations ranging from 10.60 µM to 50.86 µM. The compounds were also noncytotoxic in the mouse macrophage cell line (RAW 264.7) at 25 µg/ml concentration. Molecular docking studies were carried out against M.tb thymidylate kinase to gain insights into the binding modes of the compounds and understand the plausible mechanism of action. The compound D16 outperformed all compounds with a MIC100 of 6 µM, attributed to its strong binding affinity with thymidylate kinase valued at -9.1 kcal/mol. Compounds also showed promising activity against pathogenic bacterial and fungal strains, with the M series being more active. Even though the compounds showed broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, the inhibitory effect on the growth of Gram-positive bacteria was more significant. This may be due to the structural difference in the cell wall composition of both bacteria. Compound M9 displayed moderate to good activity against bacteria and various species of Candida. This is the first-ever report on the synthesis and biological evaluation of uracil–imine hybrids as antitubercular and antimicrobial agents.

Triethylamine-Promoted Oxidative Cyclodimerization of 2H-Azirine-2-carboxylates to Pyrimidine-4,6-dicarboxylates: Experimental and DFT Study.

An unprecedented oxidative cyclodimerization reaction of 2H-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study and DFT calculations, the key steps of the reaction mechanism include nucleophilic addition of N,N-diethylhydroxylamine to an azirine to form an (aminooxy)aziridine, generation of an azomethine ylide, and its 1,3-dipolar cycloaddition to the second azirine molecule. The crucial condition for the synthesis of pyrimidines is generation of N,N-diethylhydroxylamine in the reaction mixture in a very low concentration, which is ensured by the slow oxidation of triethylamine with air oxygen. Addition of a radical initiator accelerated the reaction and resulted in higher yields of the pyrimidines. Under these conditions, the scope of the pyrimidine formation was elucidated, and a series of pyrimidines was synthesized.

Microbiological screening of compounds with potential anti-lep activity among new synthesis compounds of the pyrimidine series

Aim. To study the effect of new synthesized pyrimidine derivatives on the growth of Mycobacterium lufu (M. lufu) and Mycobacterium tuberculosis (M. tuberculosis) when cultivated on Shkolnikova's medium.Materials and methods. The objects of research were new synthesized derivatives of 6 samples of derivatives of pyrimidine - 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-trions under laboratory codes TAG1, TAG2, TAG3, TAG4, TAG5, TAG6 and 7 samples of 5-(getarylmethylidene)-2,4,6-pyrimidine-2,4,6(1H, 3H, 5H)-trions under the laboratory codes TAG7, TAG8, TAG9, TAG10, TAG11, TAG12, TAG13. M. lufu and M. tuberculosisH37Rv strains were used as test cultures. The antimycobacterial activity of the studied compounds was studied by the method of serial dilutions.Research results. All studied compounds were found to exhibit antimycobacterial activity. The greatest inhibitory effect against M. lufu was noted for TAG1, TAG4, TAG7, TAG12, and TAG13, which was comparable to that of the reference drug dapsone. By the nature of the inhibitory effect on the growth of M. tuberculosis, the compounds under the laboratory codes TAG 1, TAG 4, TAG 7 and TAG13 were comparable to isoniazid, and the effect of the TAG3 compound was even slightly superior to the reference drug.Conclusion. Among the studied new synthesized pyrimidine derivatives, compounds under the laboratory codes TAG1, TAG4, TAG 7 and TAG13 have the most pronounced antimicrobial activity both against M. lufu and M. tuberculosis, which allows us to consider them as the most promising substances for further research on the search for antimycobacterial, including antileprosy drugs.

Microbiological screening of compounds with potential anti-lep activity among new synthesis compounds of the pyrimidine series

Aim: To study the effect of new synthesized pyrimidine derivatives on the growth of Mycobacterium lufu (M. lufu) and Mycobacterium tuberculosis (M. tuberculosis) when cultivated on Shkolnikova’s medium.Materials and methods. The objects of research were new synthesized derivatives of 6 samples of derivatives of pyrimidine - 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-trions under laboratory codes TAG1, TAG2, TAG3, TAG4, TAG5, TAG6 and 7 samples of 5-(getarylmethylidene)-2,4,6-pyrimidine-2,4,6(1H, 3H, 5H)-trions under the laboratory codes TAG7, TAG8, TAG9, TAG10, TAG11, TAG12, TAG13. M. lufu and M. tuberculosisH37Rv strains were used as test cultures. The antimycobacterial activity of the studied compounds was studied by the method of serial dilutions.Research results. All studied compounds were found to exhibit antimycobacterial activity. The greatest inhibitory effect against M. lufu was noted for TAG1, TAG4, TAG7, TAG12, and TAG13, which was comparable to that of the reference drug dapsone. By the nature of the inhibitory effect on the growth of M. tuberculosis, the compounds under the laboratory codes TAG 1, TAG 4, TAG 7 and TAG13 were comparable to isoniazid, and the effect of the TAG3 compound was even slightly superior to the reference drug.Conclusion. Among the studied new synthesized pyrimidine derivatives, compounds under the laboratory codes TAG1, TAG4, TAG 7 and TAG13 have the most pronounced antimicrobial activity both against M. lufu and M. tuberculosis, which allows us to consider them as the most promising substances for further research on the search for antimycobacterial, including antileprosy drugs.

Synthesis and Molecular Docking Studies of a Series of Amino-Pyrimidines as Possible Anti-Cancer Agents

The pyrimidine scaffold represents one of the privileged structures in chemistry, and there has been an increase in number of studies utilizing this scaffold and its derivatives. A series of 2-amino pyrimidines were synthesized by the reaction of ketene dimethyl thio-acetals with guanidinium nitrate in presence of sodium ethoxide in ethanol under reflux condition. Spectral analysis of the final compounds has been carried out using IR, 1H NMR, 13C NMR spectroscopy and HRMS. Further, the structure of one of the derivatives 4-ethoxy-6-(naphthalen-1-yl) pyrimidin-2-amine (2d) was confirmed by single crystal X-ray diffraction technique. X-ray diffraction analysis for 2d has been reported. The crystal structure of 2d is stabilized by intermolecular N–H…N, C–H…π and π…π weak interactions. To check whether pyrimidine could be ligands for two kinases involved in cancer, docking studies were performed. Few of the compounds showed strong binding affinity with IGF1R and EGFR.

2-Anilino-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine-derived CDK2 inhibitors as anticancer agents: Design, synthesis & evaluation

Deregulation of cyclin-dependent kinase 2 (CDK2) and its activating partners, cyclins A and E, is associated with the pathogenesis of a myriad of human cancers and with resistance to anticancer drugs including CDK4/6 inhibitors. Thus, CDK2 has become an attractive target for the development of new anticancer therapies and for the amelioration of the resistance to CDK4/6 inhibitors. Bioisosteric replacement of the thiazole moiety of CDKI-73, a clinically trialled CDK inhibitor, by a pyrazole group afforded 9 and 19 that displayed potent CDK2-cyclin E inhibition (Ki = 0.023 and 0.001 μM, respectively) with submicromolar antiproliferative activity against a panel of cancer cell lines (GI50 = 0.025–0.780 μM). Mechanistic studies on 19 with HCT-116 colorectal cancer cells revealed that the compound reduced the phosphorylation of retinoblastoma at Ser807/811, arrested the cells at the G2/M phase, and induced apoptosis. These results highlight the potential of the 2-anilino-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine series in developing potent and selective CDK2 inhibitors to combat cancer.

Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia.

PDE10A is an important regulator of striatal signaling that, when inhibited, can normalize dysfunctional activity. Given the involvement of dysfunctional striatal activity with schizophrenia, PDE10A inhibition represents a potentially novel means for its treatment. With the goal of developing PDE10A inhibitors, early optimization of a fragment hit through rational design led to a series of potent pyrimidine PDE10A inhibitors that required further improvements in physicochemical properties, off-target activities, and pharmacokinetics. Herein we describe the discovery of an isomeric pyrimidine series that addresses the liabilities seen with earlier compounds and resulted in the invention of compound 18 (MK-8189), which is currently in Phase 2b clinical development for the treatment of schizophrenia.

Design and synthesis of new series of chiral pyrimidine and purine analogs as COX-2 inhibitors: Anticancer screening, molecular modeling, and in silico studies

Two series of chiral novel compounds were designed and synthesized using a one-pot double Mannich-type reaction, with pyrimidine, purine, and purine bioisosteres as a central heterocyclic scaffold with a methylamino chain as a linear core 3a-e (formula A) or a purine nucleus as a central core bearing two vicinal phenyl and different heteroaryl moieties 5a-e (formula B). The NCI selected all the designed compounds for anticancer testing against 60 distinct human cancer cell lines. Compounds 3d and 5d demonstrated strong antitumor activity against a wide range of cancers, with mean growth inhibition of 59.61% and 44.30%, respectively. Both compounds showed the highest anticancer activity against breast cancer cell lines MCF-7 (94.62%, 99.76%) and MDA-MB-468 (85.81%, 92.64%). Interestingly, almost all leukemia cell lines were sensitive to both 3d and 5d Besides, compound 3d was sensitive to all-colon, ovarian, and prostate cancer cell lines. Additionally, the IC50 values of compounds 3d and 5d against the most sensitive leukemia (HL-60 (TB)), ovarian cancer (SK-OV-3), and breast carcinoma (MCF-7) cell lines were determined to be (3d, IC50 =11.96±2.74, 9.46±2.27, and 6.68±2.14 µM) and (5d, IC50 = 17.89±2.19, 8.89±2.50, and 8.75±1.99 µM), respectively. Both compounds exhibited strong antiproliferative activity that was nearly comparable to or half that of doxorubicin (IC50 = 12.54±2.10, 7.7±0.48, and 3.34±0.21 µM) and about 2- and 3-fold better than 5-FU (IC50 = 19.99±2.81, 21.8±2.09, and 16.79±2.18 µM). A COX-2 inhibition assay was performed to assess the target compounds' ability to inhibit COX-2. Compounds 3d and 5d displayed interesting COX-2 inhibition activity, exerting IC50 values in the nanomolar range in comparison to celecoxib (IC50 = 53.76±2.05 nM). However, compound 3d exerted higher anti-COX-2 activity, with an IC50 value of 69.79±2.14 nM, than compound 5d (89.92±2.17 nM). Further, compound 3d was able to arrest cell growth at the S and G2/M phases, indicating apoptosis induction. Moreover, the molecular docking of both compounds revealed a high affinity for the COX-2 receptor, with energy scores (S) = −6.63 and −7.00 kcal/mol, which were comparable to celecoxib (S) = −6.42 kcal/mol. Besides, in silico studies of compounds 3d and 5d revealed good pharmacokinetics profiles, physicochemical features, and drug-likeness data that were nearly identical to celecoxib.

Differential Activation and Desensitization States Promoted by Noncanonical α7 Nicotinic Acetylcholine Receptor Agonists.

A series of dipicolyl amine pyrimidines (DPPs) were previously identified as potential α7 agonists by means of a calcium influx assay in the presence of the positive allosteric modulator (PAM) 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596). The compounds lack the quaternary or strongly basic nitrogens of typical nicotinic agonists. Although differing in structure from typical nicotinic agonists, based on crystallographic data with the acetylcholine binding protein, they appeared to engage the site shared by such typical orthosteric agonists. Using oocytes expressing human α7 receptors, we found that the DPPs were efficacious activators of the receptor, with currents showing rapid desensitization characteristic of α7 receptors. However, we note that the rate of recovery from this desensitization depends strongly on structural features within the DPP family. Although the activation of receptors by DPP was blocked by the competitive antagonist methyllycaconitine (MLA), MLA had no effect on the DPP-induced desensitization, suggesting multiple modes of DPP binding. As expected, the desensitized conformational states could be reactivated by PAMs. Mutants made insensitive to acetylcholine by the C190A mutation in the agonist binding site were weakly activated by DPPs. The observation that activation of C190A mutants by the DPP compounds was resistant to the allosteric antagonist (-)cis-trans-4-(2,3,5,6-tetramethylphenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide supports the hypothesis that the activity of these noncanonical agonists in the orthosteric binding sites was not entirely dependent on the classic epitopes controlling activation by typical agonists and that perhaps they may access alternative modes for promoting the conformational changes associated with activation and desensitization. SIGNIFICANCE STATEMENT: This study reports a family of nicotinic acetylcholine receptor agonists that break the rules about what the structure of a nicotinic acetylcholine receptor agonist should be. It shows that the activity of these noncanonical agonists in the orthosteric binding sites is not dependent on the classical epitopes controlling activation by typical agonists and that through different binding poses, they promote unique conformational changes associated with receptor activation and desensitization.

KOtBu-mediated transition-metal-free synthesis of pyrimidines by selective three-component coupling reactions: A mechanistic insight

A KOtBu-mediated strategy for pyrimidine synthesis via selective three-component coupling reactions has been disclosed. This chemistry, in which a series of pyrimidines (20 examples) can be prepared with moderate to excellent yields, has high potential for large-scale operation owing to its metal-free conditions, atom and step economy. According to mechanistic studies, oxidative species can be generated from KOtBu or toluene in the presence of air, which can initiate the oxidation of alcohols to aldehydes (or ketones). Meanwhile, KOtBu not only promotes the condensation-cyclization process, but also triggers the dehydrogenation of dihydropyrimidine ring.

Synthesis and evaluation of hydrazinyl-containing pyrrolo[2,3-d]pyrimidine series as potent, selective and oral JAK1 inhibitors for the treatment of rheumatoid arthritis

Selective inhibition of JAK kinases within the JAK family has been a desired goal of research in order to maximize efficacy while reducing undesired off target effect. Aiming to minimize adverse effects such as anemia, a promising new class of pyrrolo[2,3-d]pyrimidine series containing a hydrazinyl moiety were synthesized and profiled. Among them compound 8m and 8o showed the best enzymatic activity against JAK1 with IC50 value of 0.16 nM and 0.3 nM respectively, and with selectivity over JAK2 by 40.6 and 10 folds respectively. In addition, 8o had an improved PK profile and demonstrated better in vivo efficacy than Tofacitinib in CIA model.

An efficient protocol for the synthesis of new camphor pyrimidine and camphor thiazole derivatives using conventional and microwave irradiation techniques and in vitro evaluation as potential antimicrobial agents.

A series of new pyrimidines and thiazoles containing camphor moiety were synthesized under both conventional and microwave irradiation techniques. The condensation of camphor either with aminoguanidine or thiosemicarbazide gives the camphor hydrazine carboximidiamide 2 and the camphor thiosemicarbazone 3, respectively. Refluxing of 3 with chloroacetonitrile afforded the camphor thiazol-4-imine 4. Compounds 2 and 4 were used as precursors for the synthesis of target products. The reaction of 2 with different species such as arylidene malononitrile, acetylacetone, and ethyl acetoacetate gave the corresponding camphor pyrimidine derivatives 5a,b-7 while refluxing of compound 4 with different reagents e.g. aldehydes, isatin, ninhydrin, acetic anhydride, benzene sulphonyl chloride, and p-nitro-benzoyl chloride afforded the camphor thiazole derivatives 8a-d-13, respectively. A comparison between the conventional way and the eco-friendly microwave irradiation method occurred in the synthesis of the same compounds, which the latter was more efficient. The elemental analysis, FT-IR, 1H NMR, 13C NMR, and Mass spectra confirm the structures of the obtained new compounds. The potential use of some selected derivatives as antimicrobial agents was investigated and gave promising results.

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines.

The interest in organic materials exhibiting thermally activated delayed fluorescence (TADF) significantly increased in recent years owing to their potential application as emitters in highly efficient organic light emitting diodes (OLEDs). Simple modification of the molecular structure of TADF compounds through the selection of different electron-donating or accepting fragments opens great possibilities to tune the emission properties and rates. Here we present the synthesis of a series of novel pyrimidine–carbazole emitters and their photophysical characterization in view of effects of substituents in the pyrimidine ring on their TADF properties. We demonstrate that electron-withdrawing substituents directly connected to the pyrimidine unit have greater impact on the lowering of the energy gap between singlet and triplet states (ΔEST) for efficient TADF as compared to those attached through a phenylene bridge. A modification of the pyrimidine unit with CN, SCH3, and SO2CH3 functional groups at position 2 is shown to enhance the emission yield up to 0.5 with pronounced TADF activity.