Month: November 2022

Mizukami, Satoshi published the artcileIonization constants of some 4,5-substituted 2-methylpyrimidines, SDS of cas: 5472-46-8, the main research area is .

An extension of the Hammett’s equation to pyrimidines is attempted. The basic ionization constants of 4,5-substituted 2-methylpyrimidines are determined potentiometrically or spectrophotometrically. The base strengths are proportional to σm (for 5-substituent) and σp (for 4-substituent) values. A method is developed for the use of the Hammett’s equation in the elucidation of the amino-imino tautomerism and the protonation equilibrium of 4-aminopyrimidines.

Journal of Organic Chemistry published new progress about Ionization. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, SDS of cas: 5472-46-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Hirai, Eizo published the artcileBehavior of 4-amino-5-carboxy-2-methylpyrimidine in aqueous solution, Safety of Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, the main research area is .

cf. CA 64, 17396e. MeI (4 ml.) added to 1 g. 4-amino-5-ethoxycarbonyl-2-methylpyrimidine in 10 ml. Me2CO, the mixture refluxed 1 hr., and the precipitate formed on cooling heated 1 hr. on a steam bath with 10 ml. 5% HI gave 0.6 g. hemihydrate of the 1-methyl betaine of 4-amino-5-carboxy-2-methylpyrimidine, decomposed 226-7° (aqueous alc.). The 1-methyl betaine of 2-aminonicotinic acid, decomposed 269-71°, and the 1-methyl betaine of 2-aminoisonicotinic acid were similarly prepared The basic ionization constants of 2-aminonicotinic acid (I) and 2-aminoisonicotinic acid (II) and of their Me and Et esters and 1-methyl betaines, and of 4-amino-5-carboxy-2-methylpyrimidine (III) and its Et ester and 1-methyl betaine were determined potentiometrically and spectrophotometrically. The basic pKa values of I and II were much lower than those calculated from the Hammett eq. I and II exist largely as zwitterions in H2O. On the basis of the uv absorption spectra of I-III as compared with those of the corresponding Et esters and 1-methyl betaines, I-III exist predominantly as zwitterions in H2O. An evaluation of the equilibrium constants between the zwitterion form and uncharged form in H2O for I and III from the Edsall and Blanchard equation (CA 27, 5233) is in agreement with this conclusion. Ir spectra of I-III in the solid state show that the compounds form an uncharged polymer linked by H bonding between the carboxyl and a nuclear N.

Chemical & Pharmaceutical Bulletin published new progress about Ionization. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, Safety of Ethyl 4-amino-2-methylpyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mizukami, Satoshi published the artcileRelation between pKa (H2O) of 5-substituted 4-amino-2-methylpyrimidines and half neutralization potential and the behavior of the compounds in nonaqueous solvents., Product Details of C8H11N3O2, the main research area is PYRIMIDINE SYSTEM; METHYLPYRIMIDINE SYSTEM; AMINOMETHYLPYRIMIDINE SYSTEM.

The half neutralization point (HNP) values and potentiometric inflections at the end point in potentiometric titrations were determined for 5-substituted 4-amino-2-methylpyrimidines (substituent = H, CH2OH, CH2NH2, CONH2, CO2Et, CO2H, CHO, or CN) in the following nonaqueous solvents: HOAc, HOAc-Me2CO, HOAc-MeCN, MeOH, EtOH, iso-PrOH, iso-PrOH-HOCH2CH2OH, Me2CO, MeCOEt, iso-BuCOMe, and MeCN. The determinations were effectively made in acidic and dipolar aprotic solvents. With some exceptions, there was a linear relation between the HNP values and the pKa (H2O) values, and between the HNP values and the Hammett σm. Deviations from these relations are discussed. Differential titration of a mixture of 5-hydroxy- and 5-formyl-4-amino-2-methylpyrimidines (I) in various solvents indicated that the power of a solvent to differentiate the mixture increased with increasing Hammett values; a dipolar aprotic solvent of low dielec. constant is recommended for titration of a mixture of the bases with HClO4. From the Hammett equation and uv spectra, these pyrimidines exist largely as the amino form in the solvents and in H2O; the true proton acceptor is the 1-position of the ring. Some abnormal results obtained with I and 5-(aminomethyl)-4-amino-2-methylpyrimidines (II) are explained by chem. reactions. II (0.15 g.) dissolved in 100 ml. Me2CO by warming at 40° or by standing 2 days gave 0.18 g.4-amino-5-(isopropylideneiminomethyl)-2-methylpyrimidine (III), leaflets, m. 151-2°. III (0.2 g.) heated 2 hrs. at 100° with 5 ml. 5% gave II.HCl and Me2CO. III (0.5 g.) in 15 ml. tetrahydrofuran treated slowly at room temperature with 0.5 g. LiAlH4, the mixture stirred 1.5 hrs., H2O added slowly to the cold mixture, and the mixture acidified with HCl gave 4-amino-5-(isopropylideneiminomethyl)-2-methyl-pyrimidine di-HCl (IV), decomposing at 284-5° (aqueous alc.). 4-Amino-5-(chloromethyl)-2-methylpyrimidine (1 g.), 3 g. (Me3)2CHNH2, and 20 ml. EtOH heated at 100° in a sealed tube 2 hrs., and the product in EtOH-Et2O treated with HCl gas gave 1.4 g. IV. A mixture of 1 g. I and 30 ml. absolute MeOH containing 4% dry HCl held 3 hrs. at room temperature and then basified with NaOMe gave 0.7 g. I di-Me acetal, m. 108.5-9° (MeOH); I di-Et acetal, m. 66-8°, was similarly prepared

Chemical & Pharmaceutical Bulletin published new progress about Ionization. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, Product Details of C8H11N3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reddy, Ambati V. Raghava published the artcileSynthesis and characterization of impurities in the production process of lopinavir, Quality Control of 192725-50-1, the main research area is lopinavir synthesis impurity; Lopinavir; Related substances; Synthesis and Characterization of impurities.

Lopinavir is an antiretroviral drug used for the inhibition of HIV protease. Four related substances of lopinavir were observed during the manufacturing process of lopinavir in the laboratory and they were identified. The present work describes the origin, synthesis, characterization, and control of these related substances.

Scientia Pharmaceutica published new progress about Impurities. 192725-50-1 belongs to class pyrimidines, name is (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, and the molecular formula is C9H16N2O3, Quality Control of 192725-50-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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