Search results for "Pyrimidines"
showing 10 items of 167 documents
Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents
2021
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…
2-Acylamino- and 2,4-bis(acylamino)pyrimidines as supramolecular synthons analysed by multiple non-covalent interactions. DFT, X-ray diffraction, and…
2012
Intermolecular interactions of ten 2-acylamino and 2,4-bis(acylamino)pyrimidines (7 of which are previously unknown) have been investigated by X-ray structural, quantum chemical (DFT), and NMR spectral methods. Especially the concentration dependencies of the (1)H NMR chemical shifts and titrations with other molecules capable of multiple hydrogen bonding provided useful information regarding their association via triple or quadruple hydrogen bonding, which is controlled by the conformational preferences of 2-acylamino- and 2,4-bis(acylamino)pyrimidines. On comparison of the properties of 2-acylamino- and 2,4-bis(acylamino)pyrimidines with the corresponding pyridines, an additional nitrogen…
Tandem Reactions of 1,2,4-Oxadiazoles with Allylamines
2011
A reaction of 3-chloro-1,2,4-oxadiazoles with allylamine and diallylamine has been investigated. 3,3a,4,5-Tetrahydroisoxazolo[3,4-d]pyrimidines are produced through a tandem ANRORC/[3 + 2]cycloaddition pathway consisting of the addition of allylamine to the 1,2,4-oxadiazole, followed by ring opening, nitrone formation, and finally cycloaddition. 3-N-Allylamino-1,2,4-oxadiazoles were also obtained as minor products through a classical SNAr. Conversely, a reaction with diallylamine produces 3-N,N-diallylamino-1,2,4-oxadiazole and imidazoline through tandem SNAr/aziridination and nucleophilic ring opening.
7-Amino-2-methylsulfanyl-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid as the dimethylformamide and water monosolvates at 293 K.
2010
The molecular structure of 7-amino-2-methylsulfanyl-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid is reported in two crystal environments, viz. as the dimethylformamide (DMF) monosolvate, C(7)H(7)N(5)O(2)S·C(3)H(7)NO, (I), and as the monohydrate, C(7)H(7)N(5)O(2)S·H(2)O, (II), both at 293 (2) K. The triazolo[1,5-a]pyrimidine molecule is of interest with respect to the possible biological activity of its coordination compounds. While the DMF solvate exhibits a layered structural arrangement through N...O hydrogen-bonding interactions, the monohydrate displays a network of intermolecular O...O and N...O hydrogen bonds assisted by cocrystallized water molecules and weak π-π stacking intera…
Heterogeneous oxidation of pyrimidine and alkyl thioethers in ionic liquids over mesoporous Ti or Ti/Ge catalysts.
2004
Heterogeneous catalytic oxidation of a series of thioethers (2-thiomethylpyrimidine, 2-thiomethyl-4,6-dimethyl-pyrimidine, 2-thiobenzylpyrimidine, 2-thiobenzyl-4,6-dimethylpyrimidine, thioanisole, and n-heptyl methyl sulfide) was performed in ionic liquids by using MCM-41 and UVM-type mesoporous catalysts containing Ti, or Ti and Ge. A range of triflate, tetrafluoroborate, trifluoroacetate, lactate and bis(trifluoromethanesulfonyl)-imide-based ionic liquids were used. The oxidations were carried out by using anhydrous hydrogen peroxide or the urea-hydrogen peroxide adduct and showed that ionic liquids are very effective solvents, achieving greater reactivity and selectivity than reactions p…
Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt
2020
A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. The synthesis of fluorinated aminopyrazoles from the same fluorinated precursor could be demonstrated but proceeded with lower efficiency.
V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…
2010
Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…
Generation of anti-azoxystrobin monoclonal antibodies from regioisomeric haptens functionalized at selected sites and development of indirect competi…
2012
Azoxystrobin is a modern strobilurin fungicide used around the world to combat prime diseases affecting highly valuable crops. Accordingly, residues of this chemical are frequently found in food, even though mostly under maximum tolerated levels. We herein describe the development of an indirect competitive immunoassay for the determination of azoxystrobin residues. A panel of monoclonal antibodies displaying subnanomolar affinity to azoxystrobin was generated using, as immunizing haptens in mice, four functionalized derivatives carrying the same spacer arm located at different rationally chosen positions. This collection of antibodies was thoroughly characterized with homologous and hetero…
Synthesis of azoxystrobin transformation products and selection of monoclonal antibodies for immunoassay development
2012
The use of agrochemicals for crop protection may result in the presence of toxic residues in soils and aquatic environments, besides in foodstuffs. Most often just the parent compound is included in the definition of pesticide residue, even though chemicals resulting from biotransformation and degradation routes might also be of toxicological relevance. Azoxystrobin is a broad-spectrum systemic fungicide widely used worldwide to combat pathogenic fungi affecting plants. We herein report the synthesis and detailed chemical characterization of several of the most relevant metabolites and degradates of azoxystrobin. These compounds were further employed as ligands for screening a collection of…
Is diabetes the cost to pay for a greater cardiovascular prevention?
2010
The recent JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) trial is another study providing evidence about the effectiveness of statin therapy in reducing cardiovascular risk. Yet, in this study significantly higher glycated hemoglobin levels and incidence rates of diabetes were observed in persons treated with rosuvastatin than the placebo group. It should be noted that adverse effects on glucose metabolism have already been reported, albeit rarely, in previous trials with statins. Although the exact mechanisms involved are unknown, it seems that statins may deteriorate glycemic control by decreasing different metabolites,…