Phenyl Pyrimidine Research Articles

Derivatives of Phenyl Pyrimidine and of the Different Donor Moieties as Emitters for OLEDs.

Two derivatives of phenyl pyrimidine as acceptor unit and triphenylamino or 4,4'-dimethoxytriphenylamino donor groups were designed and synthesized as emitters for organic light-emitting diodes (OLEDs) aiming to utilize triplet excitons in the electroluminescence. Thermogravimetric analysis revealed high thermal stability of the compounds with 5% weight loss temperatures of 397 and 438 °C. The theoretical estimations and photophysical data show the contributions of local excited and charge transfer states into emission. The addition of the methoxy groups led to the significant improvement of hole-transporting properties and the bathochromic shift of the emission from blue to green-blue spectral diapason. It is shown that mixing of the compounds with the organic host results in facilitation of the delayed emission. The singlet-triplet energy splitting was found to be too big for the thermally activated delayed fluorescence. No thermal activation of the long-lived emission was detected. No experimental evidence for triplet-triplet annihilation and room temperature phosphorescence were detected making the hot exciton mechanism the most probable one. The OLEDs based on the compounds reached the maximum external quantum efficiency of up to 10.6%.

Structure‐activity relationships for several series of fragment‐based inhibitors that target Trichomonas vaginalis nucleoside ribohydrolase enzymes

Trichomoniasis, the most common sexually transmitted infection in the world, is caused by the parasitic protozoan Trichomonas vaginalis. Upon infection, T. vaginalis has been known to cause a variety of adverse effects as well as predisposition to other illnesses. Trichomoniasis is commonly treated with 5‐nitroimidazole drugs; however, some strains have developed resistance to these drugs and novel treatments are needed. Since T. vaginalis cannot synthesize nucleobases de novo, it relies on nucleoside ribohydrolases within its pyrimidine and purine salvage pathways in order to acquire nucleobases from its host. Nucleoside ribohydrolases, such as adenosine/guanosine preferring nucleoside ribohydrolase (AGNH) and uridine nucleoside ribohydrolase (UNH), cleave the N‐glycosidic bond of purine and pyrimidine nucleosides resulting in the formation of a nucleobase and a ribose sugar. Inhibiting the AGNH or UNH enzymes would block the salvage pathway resulting in parasite cell death. Fragment screening of AGNH and UNH identified ligand‐efficient scaffolds to serve as medicinal chemistry starting points for drug design. A variety of phenyl pyridine, phenyl pyrimidine, and phenyl pyrazine compounds were then synthesized and screened for inhibitory properties. 1H and 19F NMR‐based activity assays were employed, using adenosine and 5‐fluorouridine as substrates for AGNH and UNH, respectively. It was found that compounds containing a hydroxyl group at the 2‐position resulted in lower IC50 values for AGNH, and that the UNH IC50 was lower for compounds with hydroxy or methoxy functional groups at the 2’ and 3’ positions. With the enzyme inhibition data at hand structure‐activity relationships are being derived and will be used in combination with molecular modeling to design the next generation of compounds to be synthesized. Structural data is also being pursued for both enzymes to guide compound design. Highly purified AGNH and UNH, including selenomethionine‐AGNH, have been prepared for crystallography collaborations.

Synthesis and characterization of some New 2- and 6- substituted of 5- Acetyl - 4- (P- phenyl) Pyrimidine and substituted thieno [2, 3- d] Pyrimidine

The series of new pyrimidines derivatives 2- and 6- Substituted of 5 - Acetyl - 4 - (P- phenyl) Pyrimidine and Substituted thieno [2, 3- d] Pyrimidine are synthesis by the reaction between some substituted of benzaldehydes with ethyl aceto acetate in the present of ethanol as a solvent to give the products(3e-h), when react alkyl halide with (3e-h) in ethanol obtain new Pyrimidine derivatives(4e-h) heating them with phosphorous oxy chloride in dioxane to form (5e-h) which reacts with thiourea in ethanol to produce (6e-h) these compounds reacting with chloro acetic acid to form new Substituted thieno [2,3-d] Pyrimidine (8e-h). All the synthesized compounds of new pyrimidines derivatives are identified by the physical properties by it's melting points, colors and the yields are characterized by the elemental (CHN)analysis, IR, UV Spectrum.

Biomimetic Recognition-Based Bioorthogonal Host–Guest Pairs for Cell Targeting and Tissue Imaging in Living Animals

Biomimetic Recognition-Based Bioorthogonal Host–Guest Pairs for Cell Targeting and Tissue Imaging in Living Animals

Design, Synthesis, Characterization, Computational Study and In-vitro Antioxidant and Anti-inflammatory Activities of Few Novel Pyrazol-3-one Derivatives

Aim: To design, synthesize and perform computational study on a few Novel pyrazol-3-one derivatives.
 Study design: Experimental study.
 Methodology: A series of 6-aryl substituted pyrimidine azodyes were synthesized by coupling phenyl pyrimidine 2-amine with different aromatic amines. The synthetic compounds were screened for their in-vitro antioxidant and anti-inflammatory activities. The Computational study of designed compounds was done by OCHEM, Molinspiration cheminformatics, Datawarrior, and Swiss ADME. DPPH assay was used to determine the antioxidant activity and heat hemolysis method for anti-inflammatory activity.
 Results: Molinspiration, Data Warrior, Ochem which are helpful to predict molecule general properties, bioactive scores, toxicity, and drug-likeness. Data Warrior results inferred that the compounds possess moderately active towards mutagenic (compound 2, 11), reproductive (compound 6, 7, 8), and highly active towards Tumorogenic (compound 2) toxicities. OCHEM results showed that most of the synthesized compounds were found to be non-inhibitors of all the subtypes of cytochrome P450 except compound 8. All compounds under this study were effective scavengers of free radicals except the compounds 1, 2, 6, 10. Invitro Anti-inflammatory studies have shown that the compounds (6, 7, 8, 9, 13) active toward heat hemolysis.
 Conclusion: The synthesized compounds were comprehensively studied and targets were identified rendering them as lead molecules for further development of newer agents with greater efficacy and safety.

Design, synthesis, characterization, computational study and in-vitro antioxidant and anti-inflammatory activities of few novel 6-aryl substituted pyrimidine azo dyes

A series of 6-aryl substituted pyrimidine azodyes were synthesized by coupling of phenyl pyrimidine 2-amine with different aromatic amines. The synthetic compounds were screened for their in-vitro antioxidant and anti-inflammatory activities. The characterization of the synthesized compounds was carried out by IR, 1H NMR, 13C NMR and Mass spectrophotometry. Computational study of designed compounds was done by OCHEM, Molinspiration cheminformatics, Datawarrior, and Swiss ADME. DPPH assay was used to determine the antioxidant activity and heat hemolysis method for anti-inflammatory activity.

Synthesis of New Oxazepine and Thaizolidine Compounds derived from Pyrimidine-2(2H)-one

In this paper the compounds (11-20) (methyl pyrimidine - 2(1H)-one and others phenyl pyrimidine -2(1H)- one) that will prepared from α, β unsaturated carbonyl compounds they are called chalcones, that compounds prepared from reaction of different aldehyde (4-methoxy benzaldehyde, 2-nitro benzaldehyde, 3-nitrobenzaldehyde, 4-N,N—dimethyle amino benzaldehyde, benzaldehyde, 4-nitro-benzaldehyde) with different ketones (acetone, acetophenone, 2-nitro acetophenone, 3-nitro acetophenone) after prepared this compounds and purified it and mesurment for physical, chemical and spectroscopy that we can do to get chalcones that reacted with urea under known chemical conditions to get pyrimidinone compounds we needed. pyrimidine compounds were reacted with two aromatic amines (2,4-dinitro aniline and 4- amino acetophenone) using glacial acetic acid as catalyst in absolute ethanol giving a new compounds of schiff's bases (21-40). New thiazolidine 4-one (41-50) were synthesized from reactions of Schiff's bases (21-30) with thioglycolic acid in absolute ethanol. 1,3- oxazepine derivatives. (51-60) are prepared from reaction between Schiff's bases (31-40) with malic anhydrid in absolut ethanol. The structures of the Synthesized compounds were estimated by IR, 1H- NMR and some physical data.

Structural parameters, electronic, linear and nonlinear optical exploration of thiopyrimidine derivatives: A comparison between DFT/TDDFT and experimental study

The pyrimidine ring is significantly distributed in nature due to its existence in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) as nitrogenous bases. The heterocyclic aromatic compounds have become an important pharmacophore due to promising applications in medicine and nonlinear optics (NLO) fields. Keeping in view of the significance of 4-thiopyrimidines derivatives, we selected phenyl pyrimidine derivatives namely: ethyl 4-((3-chlorobenzyl)thio)-6-methyl-2-phenylpyrimidine-5-carboxylate (1), (4-((4-chlorobenzyl)thio)-6-methyl-2-phenyl-pyrimidin-5-yl)methanol (2) and 4-((4-chlorobenzyl)thio)-5,6-dimethyl-2-phenylpyrimidine (3) for NLO study and comparative analysis. Overall, density functional theory (DFT) findings of structural parameters at B3LYP/6-311G(d,p) level show excellent concurrence with the experimental data which confirms the purity of 1, 2 and 3. The vibrational analysis of 1, 2 and 3 have been carried out by DFT calculations based on B3LYP/6-311G(d,p) level of theory. The natural bonding orbital (NBO) analysis has been used to get insight into non-covalent interactions. From DFT calculations, various parameters such as natural population analysis (NPA) atomic charges, HOMO–LUMO energies and global reactivity parameters have been obtained. The molecular electronic potential (MEP) and parametric molecular electrostatic potential (PMEP) have also been derived for 1, 2 and 3. The photophysical properties of investigated molecules were estimated using time dependent DFT (TDDFT) at B3LYP/6-311G(d,p) level of theory. Nonlinear optical (NLO) analysis has also been carried out by DFT calculations with B3LYP/6-311G(d,p) functional. The NLO properties of 1, 2 and 3 were observed larger as compared to the standard molecule indicating the considerable NLO character of all molecules especially recommended the NLO activity of 1 for optoelectronic associated hi-tech applications.

21Ne and 131Xe NMR study of electric field gradients and multinuclear NMR study of the composition of a ferroelectric liquid crystal.

This study has two goals. First, the electric field gradient (EFG) present in the liquid-crystalline phases of ferroelectric FELIX-R&D is determined using NMR spectroscopy of noble gases 21Ne and 131Xe. The 21Ne and 131Xe NMR spectra were recorded over a temperature range, which covers all the mesophases of FELIX-R&D: nematic N*, smectic A, and smectic C*. The spin quantum number of both 21Ne and 131Xe is 3/2. Their electric quadrupole moment interacts with the EFG at the nuclear site, which in liquid-crystalline phases results in the NMR spectra of the triplet structure, instead of a singlet detectable in the isotropic phase. The total EFG experienced by the noble gas nuclei consists of two contributions; one arises from the quadrupole moments of the liquid crystal molecules (external contribution) and the other one from the deformation of the electron distribution of the atoms (deformational contribution). The total EFGs determined from the 131Xe and 21Ne quadrupole splittings are very similar in the nematic and smectic A phases but differ in the smectic C* phase, being about twice larger in the 21Ne case which stems from the larger deformation of the xenon electron cloud than that of neon. For the first time, EFG was determined also in the smectic C* phase applying noble gas NMR spectroscopy. Second, the structure of molecules which, as a mixture, compose the used ferroelectric liquid crystal, FELIX-R&D, is determined by applying a number of various NMR methods and sophisticated spectral analysis. In this part, NMR spectra were recorded from FELIX-R&D/CDCl3 solution. The NMR spectral analysis was divided into four subsystems with over 13 000 000 nonzero intensity transitions. It appeared that FELIX-R&D is composed of three phenyl pyrimidine derivatives and a chiral dopant with fluorine in the asymmetric carbon atom.

Characterization of phenyl pyrimidine derivatives that inhibit cytomegalovirus immediate-early gene expression.

BackgroundPreviously, we established a reporter cell line for human cytomegalovirus and screened anti-human cytomegalovirus compounds using the cell line. In this study, we characterized one of the identified compounds, 2,4-diamino-6–(4-methoxyphenyl)pyrimidine (coded as 35C10).Methods50% Effective concentrations (EC50s) and 50% cytotoxic concentrations (CC50s) of 35C10 and its derivatives in human fibroblasts were determined by X-gal staining of the cells infected with human cytomegalovirus Towne strain expressing β-galactosidase.ResultsEC50 and CC50 of 35C10 were 4.3 µM and >200 µM, respectively. Among several 35C10 derivatives, only one lacking 4-amino group of pyrimidine showed a similar EC50. 35C10 weakly inhibited murine cytomegalovirus, herpes simplex virus type 1, and varicella-zoster virus. A “time of addition” experiment suggested that 35C10 inhibited an early phase of the infection. Although 35C10 did not inhibit viral attachment to the cells nor the delivery of viral DNA to the nuclei, it decreased the number of infected cells expressing immediate-early 1 and 2 (IE1/IE2) proteins. 35C10 also inhibited the activation of a promoter for TRL4 in the reporter cells upon human cytomegalovirus infection, but not in the same reporter cells transfected with a plasmid expressing IE2.ConclusionOur findings suggest that 35C10 is a novel compound that inhibits IE gene expression in human cytomegalovirus-infected cells.

An Efficient Synthesis of bi-Aryl Pyrimidine Heterocycles: Potential New Drug Candidates to Treat Alzheimer's Disease.

A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC50 = 0.04 ± 0.0001 μM for AChE and IC50 = 0.85 ± 0.0001 μM for BChE), the IC50 values of the synthesized compounds ranged from 3.73 ± 0.61 μM to 57.36 ± 0.22 μM for AChE and 4.81 ± 0.16 μM to 111.61 ± 0.53 μM for BChE. Among these tested compounds, 6j having a -CH3 group was found to be the most potent one against both enzymes (AChE, IC50 = 3.73 ± 0.61 μM; BChE, IC50 = 4.81 ± 0.16 μM). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.

Stable Hemiaminals: 2-Aminopyrimidine Derivatives.

Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure.

Preparation and Study of the Electro-optical Properties of Binary Mixtures of Orthoconic Anti-ferroelectric Esters and Achiral Phenyl Pyrimidine Liquid Crystal

We have prepared three different binary systems by mixing an achiral low viscous phenyl pyrimidine liquid crystalline SmC compound with three different orthoconic antiferroelectric analogous of (S)MHPOBC exhibiting SmA*-SmC*-SmCA* phase sequences. In these binary mixtures, ferroelectric and antiferroelectric phases were induced and their mesomorphic parameters (spontaneous polarization, response time, effective torsional viscosity, and anchoring energy coefficient) were determined by thermo-microscopic and electro-optical study. All the physical parameters show a nonadditive behavior with respect to the concentration of chiral mesogens due to strong dipole-dipole and/or intermolecular interactions between polar fluorinated chiral esters with heterocyclic phenyl pyrimidine compound. Interestingly the achiral mesogen reduces the response time of these binary mixtures at the cost of lower Ps. Therefore, these mixtures can be useful for high speed technological applications where low polarization, long pitch, and very fast switching ferro or anti-ferroelectric liquid crystal mixtures are desirable.

Crystal Structure Analysis of Ethyl 7-Phenyl-5- p-tolylpyrazolo[1,5-a]pyrimidine-3-carboxylate

The title compound, C22H19N3O2, was prepared from the three-component reaction. The structure of the title compound was established by single-crystal X-ray diffraction. The molecular structure shows that the phenyl ring is not coplanar with the pyrimidine ring. The torsion angle between the phenyl ring and pyrimidine ring is 147.01(15)°. The glide related molecules form one-dimensional corrugated tape-like structure via C–H···O hydrogen bonds along the crystallographic b-axis. These one-dimensional layers stack along the a-axis and form a corrugated layered structure and these layers are further stabilized by the weak C–H···π interactions. Also, it was found that the pyrazole moiety and p-toluyl groups of glide-related molecules are stacked through π···π interactions.

Synthesis and characterization of cyclometalated iridium(III) complexes containing pyrimidine-based ligands

New pyrimidine derivatives ( pyr) have been synthesized using palladium-catalyzed Suzuki coupling reaction. These compounds can undergo cyclometalation with iridium trichloride to form bis-cyclometalated iridium complexes, ( pyr ) 2Ir(acac) (acac = acetylacetonate; pyr = cyclometalated pyr). The substituents at the both cyclometalated phenyl ring and pyrimidine ring were found to affect both electrochemical and photophysical properties of the complexes. Computation results on these complexes are consistent with the electrochemical and photophysical data. The complexes are green-emitting with good solution quantum yields at ∼0.30. Light-emitting devices using these complexes as dopants were fabricated, and the device performance at 100 mA/cm 2 are moderate: 9 (17 481 cd/m 2, 4.8%, 18 cd/A, 5.1 lm/W); 10 (18 704 cd/m 2, 4.9%, 18.9 cd/A, 4.7 lm/W); 13 (20 942 cd/m 2, 5.4%, 21.0 cd/A, 6.1 lm/W).

Chain versus dimer contacts in crystalline 5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine radicals: Choices among competing intermolecular exchange mechanisms

5-(4-[N-Tert-butyl-N-aminoxyl]phenyl)pyrimidine crystallographically exhibits alternating chains and in-plane dimers involving two distinct molecular geometries, plus dimeric stacking of only one of the forms. Its magnetic behavior is neither fully spin pairing nor chain-like, but rather shows low temperature spin pairing for half of molecules in the unit cell with J/k = (−)130 J/mol, consistent with dominating exchange behavior of the dimerically π-stacked form. The other molecules in the unit cell behave in an essentially paramagnetic manner.

Manganese(II) and copper(II) hexafluoroacetylacetonate 1:1 complexes with 5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine: regiochemical parity analysis for exchange behavior of complexes between radicals and paramagnetic cations.

Mn(hfac)(2) and Cu(hfac)(2) form coordination complexes with 5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine, PyrimPh-NIT. (Mn[PyrimPh-NIT](hfac)(2))(2) and (Cu[PyrimPh-NIT](hfac)(2))(2), 1 and 2, respectively, are cyclic M(2)L(2) dimers that exhibit strong exchange coupling between the coordinated paramagnetic dication (M) and nitroxide (NIT) unit. The M-NIT exchange is strongly antiferromagnetic (AFM) in 1 and strongly ferromagnetic (FM) in 2. Magnetic susceptibility measurements for 1 were fitted to an AFM spin pairing model with J/k = -0.25 K between Mn-NIT spin sites units. Complex 2 also exhibits AFM spin pairing between S = 1 Cu-NIT spin units that is somewhat field dependent at low temperature. The fit of corrected paramagnetic susceptibility chi(T) to an AFM spin pairing model at 200 Oe yields J/k = (-)3.8 K, quite similar to earlier measurements at 1000 Oe yielding J/k = (-)5.0 K. At 1.40 K, the magnetization of 2 does not approach saturation until somewhat above 170 kOe, giving an S-shaped curve; at 0.55 K, the magnetization curve shows steps characteristic of field-induced crossover between the S = 0 ground state and excited spin states. From the steps in the 0.55 K data, we estimate J/k = (-)3.8-4.0 K for 2, in good agreement with the analysis of chi(T).

1:1 complexes of 5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine with manganese(II) and copper(II) hexafluoroacetonylacetonate.

Mn(hfac)2 and Cu(hfac)2 form 1:1 complexes with 5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine that exhibit strong metal-nitroxide exchange; spin polarization models do not explain the antiferromagnetic exchange behavior between spin sites in these complexes.

Substituent effects in carbon-nitrogen cleavage of thiamin derivatives. Fragmentation pathways and enzymic avoidance of cofactor destruction.

The combination of thiamin and benzaldehyde can produce benzoin but also destroys thiamin. The destruction comes from fragmentation of the conjugate of thiamin and benzaldehyde undergoing a process that produces a phenyl thiazole ketone and pyrimidine. The key step in this process is cleavage of the C-N bond between the heterocycles, which occurs by an unknown mechanism. Enzymes that utilize similar intermediates do not fragment the cofactor although fragmentation is inherent to the structure. To analyze the nature of the C-N cleavage step, the rates of fragmentation of a series of phenyl-substituted N1'-methyl-2-(1-hydroxybenzyl)thiamin derivatives were determined under two sets of conditions: (1) where proton transfer in the step prior to C-N bond breaking is rate-determining and (2) where C-N bond breaking is rate-determining. The resulting rho values are 1.6 and 1.8, respectively, leading to the conclusion that C-N cleavage is insensitive to substituent effects. On the basis of these results, we conclude that cleavage occurs by a facile process that resembles the outcome of a [1,5] sigmatropic rearrangement. An enzyme may avoid the fragmentation by holding the intermediate in a conformation that prevents such a process, allowing the normal catalytic process to proceed.

Critical heat capacity at the smectic A-smectic C transition in a partially fluorinated liquid crystal

A high resolution a.c. calorimetric study of a phenyl pyrimidine derivative with one alkyl and one perfluorinated end group shows that the excess heat capacity associated with the smectic A-smectic C transition exhibits critical fluctuation behaviour that is consistent with the three-dimensional XY universality class. This is in contrast to the usual mean-field SmA-SmC behaviour and the near tricritical fluctuation behaviour reported recently in several other compounds. It is speculated that smaller than usual correlation lengths are the cause for the wide fluctuation region in this compound.