Day: November 16, 2022

Budesinsky, Zdenek published the artcileOn the synthesis of 4- and 5-pyrimidinyldiphenyl-(1-imidazolyl)methanes and their antifungal activity, Formula: C8H9BrN2O2S, the main research area is pyrimidinyldiphenylmethane imidazolyl; imidazolylpyrimidinyldiphenylmethane; fungicide imidazolylpyrimidinyldiphenylmethane; Grignard reaction pyrimidinecarboxylate.

The title compounds I (R1 = Me, SMe; R2 = Cl, Br; R3 = 1-imidazolyl) and II (R3 = 1-imidazolyl) were prepared by treating the corresponding pyrimidinyldiphenylmethanols I (R1 and R2 = as above, R3 = OH) (III) and II (R3 = OH) (IV) with thionylbisimidazole prepared in situ from SOCl2 and imidazole in MeCN solution III and IV were obtained by the Grignard reaction from the appropriately substituted Et pyrimidinecarboxylates and PhMgBr but Et 4-methyl-2-methylthio-5-pyrimidinecarboxylate gave with PhMgBr Et 1,6-dihydro-4-methyl-2-methylthio-6-phenyl-5-pyrimidinecarboxylate. 5-Bromo-2-methylthiopyrimidine failed to give Grignard’s reagent with Mg but reacted with EtMgBr yielding 5-bromo-3,4-dihydro-4-ethyl-2-methylthiopyrimidine. Three I and II were tested against Saccharomyces pasterianus, Trichophyton mentagrophytes, Candida albicans, and Aspergillus niger and showed weaker antifungal activities compared with clotrimazole.

Collection of Czechoslovak Chemical Communications published new progress about Fungicides. 74840-38-3 belongs to class pyrimidines, name is Ethyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate, and the molecular formula is C8H9BrN2O2S, Formula: C8H9BrN2O2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Garzo, G. published the artcileGas chromatographic determination of 5-alkyluracils and 5-alkyldeoxyuridines using flash methylation and glass capillary columns, Recommanded Product: 5-N-Propyluracil, the main research area is uracil uridine derivative chromatog.

A sensitive anal. method was developed for 5-alkyl-substituted deoxyuridines and their main metabolites, the corresponding uracils in body fluids. The compound to be determined was methylated by the “”flash”” methylation technique, i.e., by injecting a mixture of the compounds and trimethylanilinium hydroxide (TMAH) into the hot injector of a gas chromatograph, followed by separation of the derivatives with a suitably deactivated glass capillary column. The optimal conditions for methylation were found by studying the effect of injector temperature, residence time, and TMAH/compound molar ratio on the yield of the reaction. The optimal residence time of the sample in the injector could be set by a “”semi-splitless”” injection method.

Journal of Chromatography published new progress about Body fluid. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Recommanded Product: 5-N-Propyluracil.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Tarazon, Estefania published the artcileCirculating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection, Recommanded Product: 5-Chloro-2-(methylthio)pyrimidine, the main research area is sphingosine phosphate non invasive biomarker heart transplant rejection.

Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic anal. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p < 0.0001). S1P discriminated between patients with and without rejection: normal grafts vs. all rejecting grafts (AUC = 0.911, p < 0.0001), normal grafts vs. Grade 1 R (AUC = 0.819, p < 0.01), Grade 2 R (AUC = 0.911, p < 0.0001), Grade 3 R (AUC = 0.996, p < 0.0001). In addition, we found changes in key enzymes and receptors of S1P pathway analyzed on explanted hearts from heart failure patients. This preliminary study reveals that circulating S1P determination could be a novel approach to detect cardiac rejection, showing a robust capability for detection that improves gradually with the severity of rejection. These alterations could be relevant to better understand the involvement of calcium regulation on the pathophysiol. of rejection. Scientific Reports published new progress about Biomarkers. 38275-42-2 belongs to class pyrimidines, name is 5-Chloro-2-(methylthio)pyrimidine, and the molecular formula is C5H5ClN2S, Recommanded Product: 5-Chloro-2-(methylthio)pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xu, Ming-Yuan published the artcileMetabolomic biomarkers in urine of rats following long-term low-dose exposure of cadmium and/or chlorpyrifos, COA of Formula: C5H7N3, the main research area is urine metabolomic biomarker cadmium chlorpyrifos exposure; Biomarker; Insecticide; Long-term exposure; Rat; Toxic metal; Urine.

Heavy metals and pesticides can be easily enriched in food chains and accumulated in organisms, thus pose significant threat to human health. However, their combined effects for long-term exposure at low dose has not been thoroughly investigated; especially there was no biofluid biomarker available to noninvasively diagnose the toxicosis of the combined exposure of the two chems. at their low levels. In this study, we investigated the change of urine metabolites of rats with 90-day exposure to heavy metal cadmium (Cd) and/or organophosphorus pesticide chlorpyrifos (CPF) using gas chromatog.-mass spectrometry (GC-MS)-based metabolomics approach. Our results showed that the interaction of Cd and CPF mainly displayed an antagonistic effect. We identified the panels of metabolite biomarkers in urine: benzoic acid and mannose were unique biomarkers for Cd exposure; creatinine and N-phenylacetyl glycine were unique biomarkers for CPF exposure; anthranilic acid, ribitol, and glucose were unique biomarkers for Cd plus CPF exposure. Our results suggest that 90-day exposure to Cd and/or CPF could cause a disturbance in energy and amino acid metabolism And urine metabolomics anal. can help understand the toxicity of low dose exposure to mixed environmental chems.

Ecotoxicology and Environmental Safety published new progress about Biomarkers. 22433-68-7 belongs to class pyrimidines, name is 4-Amino-5-methylpyrimidine, and the molecular formula is C5H7N3, COA of Formula: C5H7N3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Berhane, Ilyas published the artcileThieno[2,3-d]pyrimidine-Based Positive Allosteric Modulators of Human Mas-Related G Protein-Coupled Receptor X1 (MRGPRX1), Application In Synthesis of 439692-55-4, the main research area is MRGPRX1 pos allosteric modulator neuropathic pain analgesic.

Mas-related G protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and potential target for the treatment of pain. Pos. allosteric modulators (PAMs) of MRGPRX1 have the potential to preferentially activate the receptors at the central terminals of primary sensory neurons and minimize itch side effects caused by peripheral activation. Using a high-throughput screening (HTS) hit, a series of thieno[2,3-d]pyrimidine-based mols. were synthesized and evaluated as human MRGPRX1 PAMs in HEK293 cells stably transfected with human MrgprX1 gene. An iterative process to improve potency and metabolic stability led to the discovery of orally available 6-(tert-butyl)-5-(3,4-dichlorophenyl)-4-(2-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine (1t), which can be distributed to the spinal cord, the presumed site of action, following oral administration. In a neuropathic pain model induced by sciatic nerve chronic constriction injury (CCI), compound 1t (100 mg/kg, po) reduced behavioral heat hypersensitivity in humanized MRGPRX1 mice, demonstrating the therapeutic potential of MRGPRX1 PAMs in treating neuropathic pain.

Journal of Medicinal Chemistry published new progress about Analgesics. 439692-55-4 belongs to class pyrimidines, name is Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, and the molecular formula is C10H11ClN2S, Application In Synthesis of 439692-55-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sangion, Alessandro published the artcilePBT assessment and prioritization of contaminants of emerging concern: Pharmaceuticals, Product Details of C6H7FN2O2, the main research area is persistence bioaccumulation toxicity assessment prioritization contaminant emerging concern pharmaceutical; PBT; Pharmaceuticals; Prioritization; QSAR; Screening.

The strong and widespread use of pharmaceuticals, together with incorrect disposal procedures, has recently made these products contaminants of emerging concern (CEC). Unfortunately, little is known about pharmaceuticals’ environmental behavior and ecotoxicity, so that EMEA (European Medicines Agency) released guidelines for the pharmaceuticals’ environmental risk assessment. In particular, there is a severe lack of information about persistence, bioaccumulation and toxicity (PBT) of the majority of the thousands of substances on the market. Computational tools, like QSAR (Quant. Structure Activity Relationship) models, are the only way to screen large sets of chems. in short time, with the aim of ranking, highlighting and prioritizing the most environmentally hazardous for focusing further exptl. studies. In this work we propose a screening method to assess the potential persistence, bioaccumulation and toxicity of more than 1200 pharmaceutical ingredients, based on the application of two different QSAR models. We applied the Insubria-PBT Index, a MLR (Multiple Linear Regression) QSAR model based on four simple mol. descriptors, implemented in QSARINS software, and able to synthesize the PBT potential in a unique cumulative value and the US-EPA PBT Profiler that assesses the PBT behavior evaluating sep. P, B and T. Particular attention was given to the study of Applicability Domain in order to provide reliable predictions. An agreement of 86% was found between the two models and a priority list of 35 pharmaceuticals, highlighted as potential PBTs by consensus, was proposed for further exptl. validation. Moreover, the results of this computational screening are in agreement with preliminary exptl. data in the literature. This study shows how in silico models can be applied in the hazard assessment to perform preliminary screening and prioritization of chems., and how the identification of the structural features, mainly associated with the potential PBT behavior of the prioritized pharmaceuticals, is particularly relevant to perform the rational a priori design of new, environmentally safer, pharmaceuticals.

Environmental Research published new progress about Analgesics. 56177-80-1 belongs to class pyrimidines, name is 2-Ethoxy-5-fluoropyrimidin-4(3H)-one, and the molecular formula is C6H7FN2O2, Product Details of C6H7FN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Strekowski, L. published the artcileNucleotide analogs. Alkylation of 2,4-dioxopyrimidine derivatives with Mannich bases, Quality Control of 19030-75-2, the main research area is alkylation uracil thymine; uracil alkylation Mannich base; thymine alkylation Mannich base; Mannich base uracil alkylation.

Alkylation of I (R1 = H, Me, Et, Pr, Bu, Br, F, R2 = H) with the Mannich bases R2NMe2 (R2 = PhCOCH2CH2, 3-indolylmethyl) gave the N-1-monoalkylated derivatives in 11-80% yields. Condensation of thymine with 2,3-(HO)MeC6H3CH2NMe2 gave both the N-3-mono and N-1,N-3-disubstituted derivatives

Prace Wydzialu Matematyki, Fizyki i Chemii, Uniwersytet im. Adama Mickiewicza w Poznaniu, Seria: Chemia published new progress about Alkylation. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Quality Control of 19030-75-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Abraham, Michael H. published the artcileCorrelation and Estimation of Gas-Chloroform and Water-Chloroform Partition Coefficients by a Linear Free Energy Relationship Method, Name: Ethyl pyrimidine-2-carboxylate, the main research area is partition coefficient chloroform gas water estimation; linear free energy relationship partition coefficient; lipophilicity partition coefficient chloroform gas water; drug design partition coefficient chloroform gas water.

A linear free energy relation, LFER, has been used to correlate 150 values of gas-chloroform partition coefficients, as log Lchl with a standard deviation, sd, of 0.23 log units, a correlation coefficient r2 of 0.985, and an F-statistic of 1919. The equation reveals that bulk chloroform is dipolar/polarizable, of little hydrogen-bond basicity, but as strong a hydrogen-bond acid as bulk methanol or bulk ethanol. However, the main influence on gaseous solubility in chloroform is due to solute-solvent London dispersion interactions. A slightly modified LFER has been used to correlate 302 values of water-chloroform partition coefficients, as log Pchl. The correlation equation predicts log Pchl for a further 34 compounds not used in the equation with sd = 0.17 log units. When the LFER is applied to all 335 log Pchl values, the resulting equation has sd = 0.25, r2 = 0.971, and F = 2218. The importance of these results lies in the recent use of the water-chloroform system as a measure of solute lipophilicity and of recent calculations of the transfer of nucleic acids from water to chloroform. Furthermore if the water-chloroform system is to be generally used as a measure of solute lipophilicity in drug design, it will be of very considerable help to have a predictive procedure available. The authors have shown that the multiple linear regression anal. (MLRA) method is capable of correlating log Pchl values rather better than computational methods although the present MLRA method suffers from the possible lack of availability of the required descriptors.

Journal of Pharmaceutical Sciences published new progress about Drug design. 42839-08-7 belongs to class pyrimidines, name is Ethyl pyrimidine-2-carboxylate, and the molecular formula is C7H8N2O2, Name: Ethyl pyrimidine-2-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Van der Does, L. published the artcileDerivatives of pyrimidine. XXVII. Bromination of pyrimidine in the gas phase, Safety of 2,4,6-Tribromopyrimidine, the main research area is bromination pyrimidine gas phase; bromopyrimidine; aminopyrimidine.

The gas-phase bromination of pyrimidine gives 5-bromo-, 4,6-dibromo-, 2,4,6-tribromo- and 4-aminopyrimidine depending on the temperature and presence of a contact substance. Thus, pyrolysis of pyrimidine-Br at 220° gave 5% 5-bromopyrimidine and 40% 4-aminopyrimidine, whereas at 220° with pumice, only 60% 5-bromopyrimidine was found. Empty-tube pyrolysis gave Br attack at the pos.-charged positions, whereas the presence of pumice caused attack at C-5, the least-charged position.

Tetrahedron Letters published new progress about Bromination. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Safety of 2,4,6-Tribromopyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Smagowicz, J. published the artcileThe phosphorescence of hindered aminopyrimidines, HPLC of Formula: 22433-68-7, the main research area is phosphorescence aminopyridimidine; pyrimidine alkyl amino phosphorescence; alkylpyrimidine phosphorescence.

The quantum yields, lifetimes, and polarizations of phosphorescence of 4- and 5-aminopyrimidines and their hindered alkyl derivatives were measured in solvents of different polarity at 90°K. The model presented for interpretation of these data allows determining the matrix elements of spin-orbit coupling between the emitting singlet and triplet states. These elements are 0.2-0.8 cm-1 in aminopyrimidines and increase as the amino group becomes more twisted relative to the ring. Spin-orbit coupling of higher 1(n,π*) states with emitting triplets is âˆ?0 times stronger than that of the lowest 1(l,aπ*).

Journal of Luminescence published new progress about Amino group. 22433-68-7 belongs to class pyrimidines, name is 4-Amino-5-methylpyrimidine, and the molecular formula is C5H7N3, HPLC of Formula: 22433-68-7.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia