Month: November 2022

Yamashita, Junichi published the artcileStudies on antitumor agents. V. Syntheses and antitumor activities of 5-fluorouracil derivatives, SDS of cas: 56177-80-1, the main research area is uracil fluoro derivative preparation antitumor; fluorouracil derivative preparation antitumor.

Six types of 5-fluorouracil (5-FU) derivatives were synthesized; namely, 2,4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1,3-disubstituted, 1-substituted and 3-substituted compounds Thus, 2,4-dichloro-5-fluoropyrimidine was treated with BuONa in BuOH to give 2,4-dibutoxy-5-fluoropyrimidine. After oral administration of these compounds to rats, the blood levels of 5-FU were determined Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4(1H)-pyrimidone and 2-benzyloxy-5-fluoro-4(1H)-pyrimidone, were as effective as Thf-FU. The activities of 2,4-di-O-substituted derivatives, 2,4-dibutoxy-5-fluoropyrimidine and 2,4-dibenzyloxy-5-fluoropyrimidine, against Ehrlich carcinoma and against sarcoma 180, resp., were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil, were found to be as effective as Thf-FU.

Chemical & Pharmaceutical Bulletin published new progress about Antitumor agents. 56177-80-1 belongs to class pyrimidines, name is 2-Ethoxy-5-fluoropyrimidin-4(3H)-one, and the molecular formula is C6H7FN2O2, SDS of cas: 56177-80-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rode, W. published the artcileInhibition of mammalian tumor thymidylate synthetase by 5-alkylated 2′-deoxyuridine 5′-phosphates, Related Products of pyrimidines, the main research area is alkylated deoxyuridine phosphate tumor; thymidylate synthetase inhibition tumor.

Improved syntheses, based on Lewis acid-catalyzed nucleosidation, are described for the preparation of 5-alkyl-2′-deoxyuridines. These were converted to their 5′-phosphates with the use of wheat shoot phosphotransferase. The dUMP analogs 5-ethyl-dUMP  [56576-83-1] and 5-propyl-dUMP  [64374-82-9] were competitive vs. dUMP inhibitors of thymidylate synthetase  [9031-61-2] purified from mouse L1210, Ehrlich ascites, and HeLa cells, the former being the stronger inhibitor. Both analogs bind cooperatively to each of the mouse tumor enzymes, 2 mols. of inhibitor interacting with a single enzyme mol., as reflected by the parabolic character of the replots of the slope vs. inhibitor concentrations DTMP  [365-07-1] was a stronger inhibitor of the mouse tumor enzymes than its higher alkyl homologs.

Biochemical Pharmacology published new progress about Antitumor agents. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Related Products of pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Jeanrenaud, Alexander C. S. N. published the artcileCharacterisation of the epigenetic architecture of the major malaria vector Anopheles arabiensis (Diptera: Culicidae) after treatment with epigenetic modulators and heavy metals, Synthetic Route of 58366-64-6, the main research area is Anopheles arabiensis heavy metal epigenetic modulator treatment; Anopheles arabiensis; Epigenetics; Histones; Insecticide resistance; Methylation.

Anopheles arabiensis (a member of the An. gambiae species complex) is a major vector of malaria in sub-Saharan Africa. Despite its disease vector status, there is currently a paucity of epigenetic information for this species. The aim this study was therefore to analyze global epigenetic markers and their response to metal exposure in insecticide susceptible and resistant laboratory strains of An. arabiensis. This was done using com. available epigenetic marker quantification kits. In order to validate the efficacy of the kits, several kits were assessed to determine whether changes induced by known epigenetic modulators were detectable using these platforms. The efficacy of the dosages used were determined by examining the effect of the dosages used on insecticide resistant phenotypes. Upon confirmation that the dosages used were sufficient to induce a phenotypic change, the effect on epigenetic markers was assessed. Com. kits were used to quantify 5-methylcysteine (5-mC) and 5-hydroxymethylcysteine (5-hmC) methylation in DNA, m6A methylation in mRNA as well as Histone Acetyl Transferase (HAT) activity. There was a marked difference in the phenotypic response in adult mosquitoes of the insecticide susceptible strain compared to that of its’ resistant counterpart. For males and females of the resistant strain, exposure to nucleic acid modifying drugs typically increased their tolerance to insecticides. The patterns of changes in 5-mC methylation by epigenetic modulators was congruent with previous studies which quantified by mass spectrometry. The two strains differed in methylation patterns under control conditions and responded differentially to larval metal exposure. In the resistant strain, which previously was demonstrated to show increased detoxification enzyme activity and insecticide tolerance after the same treatment, the potential increase in transcriptional activity appeared to be modulated by reduced methylation and increased HAT activity. This study suggests that the com. epigenetic quantification kits can be used to characterize phenotypic changes in An. arabiensis, and also shows that epigenetic regulation of the response to metal exposure is regulated at the DNA as opposed to the RNA level.

Acta Tropica published new progress about Adult, mammalian. 58366-64-6 belongs to class pyrimidines, name is 5-Methylcytosinehydrochloride, and the molecular formula is C5H8ClN3O, Synthetic Route of 58366-64-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Arnett, Edward M. published the artcileSolvent effects in organic chemistry. VIII. Acidity function failure in different aqueous acids, Formula: C8H11N3O2, the main research area is .

cf. CA 62, 13908d. Acidity functions (H0′, H0”’, and HR) are given for primary and tertiary aromatic amines and triarylcarbinols in aqueous HCl, H3PO4, and p-toluenesulfonic acids. In all of these media, and H2SO4, the order in which the acidity functions change with acid concentration is HR > HR’ > H0”’ > H0′. Using such functions as H0”’ – H0′ (i.e., log fB’fB”’H+/fB’H+fB”’) as a criterion of acidity function failure, it is found that these terms have a roughly linear relationship to the acid molarity in these media and in HClO4, but give variously shaped curves if plotted against log aH2O. The slopes of the linear Sechenov-like plots for (HR’ – H0′) in these acids fall in the order HClO4 > H2SO4 > HePO4 > HCl, suggesting that H2SO4 and HClO4 are the worst media of the four as far as acidity function failure is concerned. The importance of factors (such as size) other than ion hydration in determining activity coefficient and, hence, acidity functions is noted. It is suggested that the failure of rates of acid-catalyzed reactions to give linear plots of log k1 vs. H0 of unit slope be treated in a similar way. Plots of (log k1 + H0) vs. molarity of acid are linear over a fair range of acidity in conformity with the Sechenov-like equation log fSfBH+ /f*fB = constant × molarity. Aqueous solutions of p-toluenesulfonic acid give a medium in which H0′ and H0”’ are very close together and might be a useful one for acidity function work. However, the solutions are only weakly acidic compared to the mineral acids and present a very limited range of acidities.

Journal of the American Chemical Society published new progress about Acidity function. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, Formula: C8H11N3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Padmaja, N. published the artcileStructure of 5-methylcytosine hydrochloride, Synthetic Route of 58366-64-6, the main research area is mol structure methyl cytosine hydrochloride.

The title compound is monoclinic, space group P21/c, with a 6.431(1), b 16.132(2), c 7.030(1) Å, and β 97.33(1)°; dc = 1.48 and dm = 1.49 for Z = 4. The final R = 0.042 for 1146 reflections. At. coordinates are given. The cytosine base is protonated at N(3). The structure is stabilized by H bonds of the type N(3)-H…Cl and direct electrostatic interactions between Cl and atoms of the base. Mols. related by the c-glide are nearly parallel and are separated by ∼3.5 Å. A comparison of the stacking interactions observed in the present structure and in related mols. suggests that 5-methylation of the cytosine base generally results in reduced ring overlap.

Acta Crystallographica, Section C: Crystal Structure Communications published new progress about Crystal structure. 58366-64-6 belongs to class pyrimidines, name is 5-Methylcytosinehydrochloride, and the molecular formula is C5H8ClN3O, Synthetic Route of 58366-64-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gardner, Evan J. published the artcileTris(pyrazolyl)borate Copper Hydroxide Complexes Featuring Tunable Intramolecular H-Bonding, Recommanded Product: Ethyl pyrimidine-2-carboxylate, the main research area is crystal structure copper pyrazolylborate pendant heterocycle arm; copper pyridyl pyrimidyl pyrazolylborate preparation intramol hydrogen bonding.

A modular synthesis provides access to new tris(pyrazolyl)borate ligands XpyMeTpK that possess a single functionalized pendant pyridyl (py) or pyrimidyl (pyd) arm designed to engage in tunable intramol. H-bonding to metal-bound functionalities. To illustrate such H-bonding interactions, [XpyMeTpCu]2(μ-OH)2 (6a-6e) complexes were synthesized from the corresponding XpyMeTpCu-OAc (5a-5e) complexes. Single crystal x-ray structures of three new dinuclear [XpyMeTpCu]2(μ-OH)2 complexes reveal H-bonding between the pendant heterocycle and bridging hydroxide ligands while the donor arm engages the Cu center in an unusual monomeric DMAPMeTpCu-OH complex. Vibrational studies (IR) of each bridging hydroxide complex reveal reduced νOH frequencies that tracks with the H-bond accepting ability of the pendant arm. Reversible protonation studies that interconvert [XpyMeTpCu]2(μ-OH)2 and [XpyMeTpCu(OH2)]OTf species indicate that the acidity of the corresponding aquo ligand decreases with increasing H-bond accepting ability of the pendant arm.

Inorganic Chemistry published new progress about Crystal structure. 42839-08-7 belongs to class pyrimidines, name is Ethyl pyrimidine-2-carboxylate, and the molecular formula is C7H8N2O2, Recommanded Product: Ethyl pyrimidine-2-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sharma, Lalit Kumar published the artcileLipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators, Related Products of pyrimidines, the main research area is isopropylphenyl pyridazine derivative panthothenate kinase lipophilic ligand efficiency; Hit-to-lead; Lipophilic ligand efficiency; Pantothenate Kinase; Pyridazine.

Pantothenate kinase (PANK) is the critical regulator of intracellular levels of CoA and has emerged as an attractive target for treating neurol. and metabolic disorders. This report describes the optimization, synthesis, and full structure-activity relationships of a new chem. series of pantothenate competitive PANK inhibitors. Potent drug-like mols. were obtained by optimizing a high throughput screening hit, using lipophilic ligand efficiency (LipE) derived from human PANK3 IC50 values to guide ligand development. X-ray crystal structures of PANK3 with index inhibitors from the optimization were determined to rationalize the emerging structure activity relationships. The anal. revealed a key bidentate hydrogen bonding interaction between pyridazine and R306′ as a major contributor to the LipE gain observed in the optimization. A tractable series of PANK3 modulators with nanomolar potency, excellent LipE values, desirable physicochem. properties, and a well-defined structural binding mode was produced from this study.

Bioorganic & Medicinal Chemistry published new progress about Crystal structure. 38275-56-8 belongs to class pyrimidines, name is 5-Chloropyrimidine-2-carbonitrile, and the molecular formula is C5H2ClN3, Related Products of pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Knoblauch, Bernd H. A. published the artcile5-substituted UTP derivatives as P2Y2 receptor agonists, Product Details of C7H10N2O2, the main research area is UTP analog preparation phosphorylation structure activity; uracil nucleotide crystal structure; purinergic P2Y2 receptor antagonist uracil nucleotide.

A series of 5-alkyl-substituted UTP derivatives, which had been synthesized previously with a moderate degree of purity, was resynthesized, purified, and characterized. Synthetic and purification procedures were optimized. New spectroscopic data, including 13C- and 31P NMR data, are presented. Phosphorylation reactions yielded a number of side products, such as the 2′-, 3′-, and 5′-monophosphates, the 2′,3′-cyclic monophosphates, and the 2′,3′-cyclic phosphates of the 5′-triphosphates. Furthermore, raw products were contaminated with inorganic phosphates, including cyclometatriphosphate, phosphate, and pyrophosphate. The uracil nucleotides were investigated for their potency to increase intracellular calcium concentrations by stimulation of P2Y2 receptors (P2Y2R) on NG108-15 cells, a mouse neuroblastoma × glioma cell line, and in human basal epithelial airway cells, including a cystic fibrosis (CF/T43) cell line. UTP exhibited EC50 values of ca. 1 μM (in NG108-15 cells) and of 0.1 μM (in CF/T43 cells), resp. 5-Substituted UTP derivatives were agonists at the P2Y2R, but were less potent than UTP. 5-Ethyl-UTP, for example, exhibited an EC50 value of 99 μM at P2Y2R of NG108-15 cells and proved to be a full agonist. With increasing volume of the 5-substituent of UTP derivatives, P2Y2 activity decreased.

European Journal of Medicinal Chemistry published new progress about Crystal structure. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Product Details of C7H10N2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sandosham, Jessie published the artcileSyntheses of 5-alkenylpyrimidines by organotin reactions, HPLC of Formula: 84755-30-6, the main research area is stannylpyrimidine preparation coupling alkenyl bromide; vinylpyrimidine; alkenylpyrimidine; halopyrimidine coupling vinyltin; pyrimidine alkenyl.

5-Stannylpyrimidine I (R = SnBu3) (II) was prepared from I (R = Br) by lithiation at -95° and quenching with Bu3SnCl. II is used in Pd-catalyzed coupling reactions with vinyl bromides to give 5-vinylpyrimidines I (R = CH:CHR1, R1 = H, Me, Ph). The opposite reaction sequence, i.e. Pd-catalyzed coupling between 5-halopyrimidines and vinyltin derivatives, is also described. Alternatively, the 5-vinylpyrimidines have been obtained by dehydrohalogenation with CsF and by a modified Wittig reaction. 2-Methylthiopyrimidines are transformed into the 2-methoxy derivatives or 2-pyrimidinones using chloramine-T in a simple one-pot synthesis.

Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry published new progress about Coupling reaction. 84755-30-6 belongs to class pyrimidines, name is 4-Methyl-2-(methylthio)pyrimidine-5-carbaldehyde, and the molecular formula is C7H8N2OS, HPLC of Formula: 84755-30-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Henriksen, Ulla published the artcileFacile synthesis of N-(1-alkenyl) derivatives of 2,4-pyrimidinediones, Application In Synthesis of 19030-75-2, the main research area is pyrimidinedione alkenyl derivative synthesis.

N-(1-alkenyl) derivatives of 2,4-pyrimidinediones were prepared in a one pot synthesis from aldehydes and the nucleobases using trimethylsilyl trifluoromethanesulfonate (TfOTMS) as coupling reagent. Presilylation of the above nucleobases, and N6-benzoyladenine, with excess N,O-bis(trimethylsilyl)acetamide (BSA) followed by addition of one mol eq. TfOTMS yielded the N-(1-trimethylsilyloxyalkyl) derivatives

Nucleosides, Nucleotides & Nucleic Acids published new progress about Coupling reaction. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Application In Synthesis of 19030-75-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia