Category: pyrimidines

Gorska, Katarzyna published the artcileLigand dimerization programmed by hybridization to study multimeric ligand-receptor interactions, Quality Control of 186046-81-1, the publication is Chemical Communications (Cambridge, United Kingdom) (2010), 46(41), 7742-7744, database is CAplus and MEDLINE.

Oligomerization of receptors induced or stabilized by polyvalent ligands is a fundamental mechanism in cellular recognition and signal transduction. Herein we report a general approach to encode complex peptide macrocycles with peptide nucleic acid (PNA) tags and program their oligomerization through hybridization as exemplified with a ligand binding to oligomeric DR5, a receptor of TRAIL cytokine.

Chemical Communications (Cambridge, United Kingdom) published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Quality Control of 186046-81-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Wang, Li-zhong published the artcileSynthesis of 9-ethylguanine, Related Products of pyrimidines, the publication is Huaxue Shiji (2016), 38(2), 189-192, database is CAplus.

Starting from di-Et malonate and guanidine hydrochloride, condensation in basic conditions gave the intermediate 2-amino-4,6-dihydroxypyrimidine. Then, in the presence of triethylamine as the acid-trapping agent and at a temperature of 80°C, 2-amino-6-chloropyrimidin-4(3H)-one was prepared by an excess of phosphorus oxychloride and the decomposition of sodium hydroxide, and then after ethylamino, nitrosation and cyclization, obtain the target product. Though optimizing the reaction conditions, the optimal parameters are obtained. The reaction route is simple, feasible process routes. The product through the m.p., IR, ¹HNMR and ¹³CNMR was confirmed.

Huaxue Shiji published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C38H74Cl2N2O4, Related Products of pyrimidines.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Grieco, Ilenia published the artcileDeveloping novel classes of protein kinase CK1δ inhibitors by fusing [1,2,4]triazole with different bicyclic heteroaromatic systems, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is European Journal of Medicinal Chemistry (2021), 113331, database is CAplus and MEDLINE.

New series of [1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-a][1,3,5]triazines was developed. Some crucial interactors have been identified, such as the presence of a free amino group able to interact with the residues of the hinge region at the 5- and 7- positions of the [1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-a][1,3,5]triazine scaffolds, resp.; or the presence of a 3-hydroxyphenyl or 3,5-dihydroxyphenyl moiety at the 2- position of both nuclei. Mol. modeling studies identified the key interactions involved in the inhibitor-protein recognition process that appropriately fit with the outlined structure-activity relationship. Considering the fact that the CK1 protein kinase is involved in various pathologies in particular of the central nervous system, the interest in the development of new inhibitors permeable to the blood-brain barrier represents today an important goal in the pharmaceutical field. The best potent compound of the series is the 5-(7-amino-5-(benzylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)benzen-1,3-diol (IC₅₀ = 0.18μM) that was predicted to have an intermediate ability to cross the membrane in vitro assay and represents an optimal starting point to both studies the therapeutic value of protein kinase CK1δ inhibition and to develop new more potent derivatives

European Journal of Medicinal Chemistry published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Shaikh, Ashif Y. published the artcileOptimized synthesis of Fmoc/Boc-protected PNA monomers and their assembly into PNA oligomers., Quality Control of 169396-92-3, the publication is European Journal of Organic Chemistry (2021), 2021(19), 2792-2801, database is CAplus.

Continuous advancement of application of peptide nucleic acid (PNA) oligomers encouraged exploration of rapid and efficient synthesis of PNA monomers and oligomers. Among the PNA monomers developed, only a few are commonly used in automated PNA synthesis. Herein, we report short and efficient protocols suitable for large-scale synthesis of Fmoc/Boc-protected PNA monomers with advantageous solubility properties; these also facilitate purification due to the traceless nature of the Boc protecting group. Initially, several coupling reagents were screened for assembly of a pentamer containing all four nucleobases, and then the most promising reagents were tested in the synthesis of a decamer. The Fmoc/Boc-protected monomers proved compatible with both manual synthesis and assembly on an automated peptide synthesizer at room temperature or at 40°C. As compared to the commonly used coupling agent, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), both 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and [ethyl cyano(hydroxyimino)acetato-O²]tri-1-pyrrolidinylphosphonium hexafluorophosphate (PyOxim) proved more favorable, with the latter being superior. A previously reported side reaction of guanine bases in the presence of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) was not observed with the phosphonium salts.

European Journal of Organic Chemistry published new progress about 169396-92-3. 169396-92-3 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide,Others,PNA, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C3H12Cl2N2, Quality Control of 169396-92-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Cao, Jian published the artcileMultiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling, Recommanded Product: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is Analytical Chemistry (Washington, DC, United States) (2021), 93(4), 2610-2618, database is CAplus and MEDLINE.

Mass-spectrometry-based chemoproteomics has enabled the rapid and proteome-wide discovery of functional and potentially ′druggable′ hotspots in proteins. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or ′click′ chem. The absence of bio-orthogonal chemistries that are functionally equivalent and complementary to CuAAC for chemoproteomic applications has hindered the development of multiplexed chemoproteomic platforms capable of assaying multiple amino acid side chains in parallel. Here, we identify and optimize Suzuki-Miyaura cross-coupling conditions for activity-based protein profiling and mass-spectrometry-based chemoproteomics, including for target deconvolution and labeling site identification. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual labeling. Multiplexed targeted deconvolution identified the protein targets of bifunctional cysteine- and lysine-reactive probes.

Analytical Chemistry (Washington, DC, United States) published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H9N3O2, Recommanded Product: 2-(Dimethylamino)pyrimidine-4,6-diol.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Rageot, Denise published the artcile(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class I PI3K and mTOR Kinase, Safety of 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, the publication is Journal of Medicinal Chemistry (2019), 62(13), 6241-6261, database is CAplus and MEDLINE.

The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is frequently overactivated in cancer, and drives cell growth, proliferation, survival, and metastasis. Here, we report a structure-activity relationship study, which led to the discovery of a drug-like ATP-site PI3K/mTOR kinase inhibitor: (S)-4-(difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, compound 6), which qualifies as a clin. candidate due to its potency and specificity for PI3K and mTOR kinases, and its pharmacokinetic properties, including brain penetration. Compound 6 showed excellent selectivity over a wide panel of kinases and an excellent selectivity against unrelated receptor enzymes and ion channels. Moreover, compound 6 prevented cell growth in a cancer cell line panel. The preclin. in vivo characterization of compound 6 in an OVCAR-3 xenograft model demonstrated good oral bioavailability, excellent brain penetration, and efficacy. Initial toxicity studies in rats and dogs qualify 6 for further development as a therapeutic agent in oncol.

Journal of Medicinal Chemistry published new progress about 944401-58-5. 944401-58-5 belongs to pyrimidines, auxiliary class Trifluoromethyl,Pyrimidine,Fluoride,Boronic acid and ester,Amine,Boronate Esters,Boronic acid and ester,, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, and the molecular formula is C11H15BF3N3O2, Safety of 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Hansen, Anna Mette published the artcileMicrowave-assisted solid-phase synthesis of antisense acpP peptide nucleic acid-peptide conjugates active against colistin- and tigecycline-resistant E. coli and K. pneumoniae, SDS of cas: 172405-16-2, the publication is European Journal of Medicinal Chemistry (2019), 134-145, database is CAplus and MEDLINE.

Recent discovery of potent antibacterial antisense PNA-peptide conjugates encouraged development of a fast and efficient synthesis protocol that facilitates structure-activity studies. The use of an Fmoc/Boc protection scheme for both PNA monomers and amino acid building blocks in combination with microwave-assisted solid-phase synthesis proved to be a convenient procedure for continuous assembly of antisense PNA-peptide conjugates. A validated antisense PNA oligomer (CTCATACTCT; targeting mRNA of the acpP gene) was linked to N-terminally modified drosocin (i.e., RXR-PRPYSPRPTSHPRPIRV; X = aminohexanoic acid) or to a truncated Pip1 peptide (i.e., RXRRXR-IKILFQNRRMKWKK; X = aminohexanoic acid), and determination of the antibacterial effects of the resulting conjugates allowed assessment of the influence of different linkers as well as differences between the L– and D-forms of the peptides. The drosocin-derived compound without a linker moiety exhibited highest antibacterial activity against both wild-type Escherichia coli and Klebsiella pneumoniae (MICs in the range 2-4 μg/mL ∼ 0.3-0.7 μM), while analogs displaying an ethylene glycol (eg1) moiety or a polar maleimide linker also possessed activity toward wild-type K. pneumoniae (MICs of 4-8 μg/mL ∼ 0.6-1.3 μM). Against two colistin-resistant E. coli strains the linker-deficient compound proved most potent (with MICs in the range 2-4 μg/mL ∼ 0.3-0.7 μM). The truncated all-L Pip1 peptide had moderate inherent activity against E. coli, and this was unaltered or reduced upon conjugation to the antisense PNA oligomer. By contrast, this peptide was 8-fold less potent against K. pneumoniae, but in this case some PNA-peptide conjugates exhibited potent antisense activity (MICs of 2-8 μg/mL ∼ 0.3-1.2 μM). Most interestingly, the antibacterial activity of the D-form peptide itself was 2- to 16-fold higher than that of the L-form, even for the colistin- and tigecycline-resistant E. coli strains (MIC of 1-2 μg/mL ∼ 0.25-0.5 μM). Low activity was found for conjugates with a two-mismatch PNA sequence corroborating an antisense mode of action. Conjugates containing D-peptide were also significantly less active. In conclusion, we have designed and synthesized antisense PNA-drosocin conjugates with potent antibacterial activity against colistin- and tigecycline-resistant E. coli and K. pneumonia without concomitant hemolytic properties. In addition, a truncated D-form of Pip1 was identified as a peptide exhibiting potent activity against both wild-type and multidrug-resistant E. coli, P. aeruginosa, and A. baumannii (MICs within the range 1-4 μg/mL ∼ 0.25-1 μM) as well as toward wild-type Staphylococcus aureus (MIC of 2-4 μg/mL ∼ 0.5-1.0 μM).

European Journal of Medicinal Chemistry published new progress about 172405-16-2. 172405-16-2 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide, name is 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, and the molecular formula is C11H15N3O5, SDS of cas: 172405-16-2.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Kosevich, M. V. published the artcileInteraction of calcium and copper ions with pyrimidine bases in frozen water solutions, COA of Formula: C5H6N2O2, the publication is Visnik Kharkivs’kogo Natsional’nogo Universitetu im. V. N. Karazina (2003), 29-39, database is CAplus.

Interaction of nucleic acid pyrimidine bases m₁³Ura, m₁¹Thy, Cyt with calcium and copper ions in frozen water solutions was studied using low temperature fast atom bombardment mass spectrometric technique. Inspection of systems with varied concentrations of bases and chlorides of the metals have shown that base-metal associates recorded in the mass spectra are connected with finely dispersed structure of the eutectic of the frozen samples. It was revealed that the rate of the interactions and types of the associates formed are dependent on the divalent metal type. Calcium ions showed higher yields of associates with the bases in the solid-frozen systems in comparison with dilute water solutions Calcium ions produced along with electrostatically bound complexes covalent ones by substitution of a proton of a base while copper ions produced only non-covalent low-abundant associates In the case of thymine base which is prone to self-association, the distinctions between calcium and copper interactions were preserved at the level of the base dimers.

Visnik Kharkivs’kogo Natsional’nogo Universitetu im. V. N. Karazina published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C5H6N2O2, COA of Formula: C5H6N2O2.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Lomoth, R. published the artcileSpectral and kinetic identification of radical cations of pyrimidine bases by stepwise electron transfer, Formula: C5H6N2O2, the publication is Chemical Physics Letters (1998), 288(1), 47-51, database is CAplus.

Radical cations of methylated derivatives of uracil and thymine were generated by electron transfer to the parent radical cation, generated in acetone by nanosecond pulse radiolysis. The resulting transient absorption peaking around 400 and 550 nm is assigned to the radical cations of the pyrimidine bases. Direct kinetic and spectroscopic evidence for this assignment has been given by a subsequent electron transfer from triphenylamine to the pyrimidine radical cations yielding the characteristic absorption spectrum of the triphenylamine radical cation.

Chemical Physics Letters published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C5H6N2O2, Formula: C5H6N2O2.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Volkov, Oleg A. published the artcileSpecies-Selective Pyrimidineamine Inhibitors of Trypanosoma brucei S-Adenosylmethionine Decarboxylase, Computed Properties of 56-05-3, the publication is Journal of Medicinal Chemistry (2018), 61(3), 1182-1203, database is CAplus and MEDLINE.

New therapeutic options are needed for treatment of human African trypanosomiasis (HAT) caused by protozoan parasite Trypanosoma brucei. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the polyamine pathway of T. brucei. Previous attempts to target this enzyme were thwarted by the lack of brain penetration of the most advanced series. Herein, the authors describe a T. brucei AdoMetDC inhibitor series based on a pyrimidineamine pharmacophore that the authors identified by target-based high-throughput screening. The pyrimidineamines showed selectivity for T. brucei AdoMetDC over the human enzyme, inhibited parasite growth in whole-cell assay, and had good predicted blood-brain barrier penetration. The medicinal chem. program elucidated structure-activity relationships within the series. Features of the series that were required for binding were revealed by determining the x-ray crystal structure of TbAdoMetDC bound to one analog. The pyrimidineamine series provides a novel starting point for an anti-HAT lead optimization.

Journal of Medicinal Chemistry published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C8H7NO4, Computed Properties of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia