Day: December 6, 2022

Lu, Xueyi published the artcileThe discovery of novel diarylpyri(mi)dine derivatives with high level activity against a wide variety of HIV-1 strains as well as against HIV-2, Related Products of pyrimidines, the publication is Bioorganic & Medicinal Chemistry (2018), 26(8), 2051-2060, database is CAplus and MEDLINE.

By structure-based mol. hybridization strategy, a series of novel diarylpyri(mi)dine derivatives targeting the entrance channel of HIV-1 reverse transcriptase (RT) were designed, synthesized and evaluated as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs). Encouragingly, all the tested compounds showed good activities against wild-type (WT) HIV-1 (IIIB) with EC₅₀ in the range of 1.36 nM-29 nM, which is much better than those of nevirapine (NVP, EC₅₀ = 125.42 nM) and azidothymidine (AZT, EC₅₀ = 11.36 nM). Remarkably, these compounds also displayed effective activity against the most of the single and double-mutated HIV-1 strains with low EC₅₀ values, which is comparable to the control drugs. Besides, these compounds were also exhibited favorable enzymic inhibitory activity. Moreover, preliminary structure-activity relationships (SARs) and mol. modeling study were investigated and discussed in detail. Unexpectedly, four diarylpyrimidines yielded moderate anti-HIV-2 activities. To the authors’ knowledge, this is rarely reported that diarylpyrimidine-based NNRTIs have potent activity against both HIV-1 and HIV-2 in cell culture.

Bioorganic & 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, Related Products of pyrimidines.

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

Jia, Guifang published the artcileOxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is FEBS Letters (2008), 582(23+24), 3313-3319, database is CAplus and MEDLINE.

The human obesity susceptibility gene, FTO, encodes a protein that is homologous to the DNA repair AlkB protein. The AlkB family proteins utilize iron(II), α-ketoglutarate (α-KG) and dioxygen to perform oxidative repair of alkylated nucleobases in DNA and RNA. We demonstrate here the oxidative demethylation of 3-methylthymine (3-meT) in single-stranded DNA (ssDNA) and 3-methyluracil (3-meU) in single-stranded RNA (ssRNA) by recombinant human FTO protein in vitro. Both human and mouse FTO proteins preferentially repair 3-meT in ssDNA over other base lesions tested. They showed negligible activities against 3-meT in double-stranded DNA (dsDNA). In addition, these two proteins can catalyze the demethylation of 3-meU in ssRNA with a slightly higher efficiency over that of 3-meT in ssDNA, suggesting that methylated RNAs are the preferred substrates for FTO.

FEBS 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, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Shigenaga, Akira published the artcileDevelopment of thiol-responsive amide bond cleavage device and its application for peptide nucleic acid-based DNA releasing system, Application In Synthesis of 169396-92-3, the publication is Tetrahedron Letters (2010), 51(18), 2525-2528, database is CAplus.

To develop a thiol-responsive DNA-releasing system, a thiol-responsive amino acid capable of inducing an amide bond cleavage in the presence of a thiol was developed. It was successfully combined with peptide nucleic acid (PNA), and thiol-induced release of DNA from the thiol-responsive PNA/DNA complex was observed

Tetrahedron Letters 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 C14H10O4, Application In Synthesis of 169396-92-3.

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

Chen, An published the artcileDesign, synthesis and biological evaluation of 2-methyl-(1,1′-biphenyl)-pyrimidine conjugates, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is Bioorganic & Medicinal Chemistry Letters (2020), 30(16), 127328, database is CAplus and MEDLINE.

Small mol. inhibitors of biphenyl structure as core backbone showed a significant effect on PD-1/PD-L1 axis, and 2-amino-pyrimidine structure is a promising privileged scaffold in medicinal chem. and drug discovery. The authors designed by combination principles and synthesized 27 novel compounds with N-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)pyrimidin-2-amine as a basic skeletal structure, and their anti-cancer activity was evaluated. Among compounds, N⁴-(3-(dimethylamino)propyl)-N²-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)-6-morpholinopyrimidine-2,4-diamine, N⁴-(3-(diethylamino)propyl)-N²-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)-6-morpholinopyrimidine-2,4-diamine, N²-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)-6-morpholino-N⁴-(3-(pyrrolidin-1-yl)propyl)pyrimidine-2,4-diamine, N²-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)-6-morpholino-N⁴-(3-(piperidin-1-yl)propyl)pyrimidine-2,4-diamine and N⁴-(3-(diethylamino)propyl)-N²-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)-6-(piperazin-1-yl)pyrimidine-2,4-diamine displayed strong anti-cancer effects on 9 tested cancer cell lines, in particular, the N⁴-(3-(diethylamino)propyl)-N²-((2-methyl-[1,1′-biphenyl]-3-yl)methyl)-6-(piperazin-1-yl)pyrimidine-2,4-diamine did the highest inhibitive activity, but against HepG2 cells, and possessed the lowest IC₅₀ value of 2.08μΜ towards HT-29 cells.

Bioorganic & Medicinal Chemistry Letters 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

Schneggenburger, Philipp E. published the artcileAzide reduction during peptide cleavage from solid support-the choice of thioscavenger?, Quality Control of 186046-81-1, the publication is Journal of Peptide Science (2010), 16(1), 10-14, database is CAplus and MEDLINE.

Peptide azides acquired growing impact because of application in bioconjugation via click chem.’ or Staudinger ligation. Furthermore, there are many methods established in organic synthesis addressing the reduction of azides to amines, but no observation of a reductive transformation of peptide azides during SPPS cleavage was yet reported. In the present study, the reduction of peptide azides during SPPS cleavage was investigated depending on the choice of thioscavenger, reacting as reductive species. First observed for short PNA/peptide conjugates the occurring extensive side reaction was also validated for one of the applied azide amino acid building blocks and was further investigated by applying different cleavage cocktails to a series of peptides varying in hydrophobicity and position of the azide moiety in the oligomer sequence. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.

Journal of Peptide Science 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

Krueger, Oliver published the artcileOxidative Cleavage of a Cyclobutane Pyrimidine Dimer by Photochemically Generated Nitrate Radicals (NO₃^•), Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Organic Letters (2001), 3(10), 1455-1458, database is CAplus and MEDLINE.

Photochem. generated nitrate radicals (NO₃•) cleave the stereoisomeric N,N-dimethyl-substituted uracil cyclobutane dimers into the monomeric uracil derivative as the major reaction pathway. The reactants thus studied were cis–syn-1,3-dimethyluracil dimer [i.e., (4aR,4bS,8aS,8bR)-rel-hexahydro-1,3,6,8-tetramethylcyclobuta[1,2-d:4,3-d‘]dipyrimidine-2,4,5,7(3H,6H)-tetrone], trans–syn-1,3-dimethyluracil dimer, cis–anti-1,3-dimethyluracil dimer, and trans-anti-1,3-dimethyluracil dimer. A preferred splitting of the syn dimers was observed The reaction is expected to proceed through initial one-electron oxidation with formation of an intermediate cyclobutane radical cation. In addition to cycloreversion, competing reaction steps of a cation radical intermediate, which lead to the observed byproducts, are suggested.

Organic 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, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Shinozuka, Kazuo published the artcileNucleoside complexing. A carbon-13 NMR spectroscopic investigation of the metal binding sites in 7-methylguanosine, 7-methylinosine and some related new synthetic betaines, Product Details of C6H9N3O2, the publication is Inorganica Chimica Acta (1985), 100(1), 141-50, database is CAplus.

A ¹³C NMR spectroscopic study of the binding of various metal species, including hard metal species (Sr, Ba, La, Pr), intermediate metal species (Zn, Cd, Pb), and soft metal species (Pt, Hg), is reported. The ¹³C NMR shift patterns for the O6 resonance of 7-methylguanosine, 7-methylinosine, 2-(dimethylamino)-7.9-dimethylhypoxanthinium betaine, 2-(diethylamino)-7-methyl-9-propylhypoxanthinium betaine, and the (ethylamino) and 6-thio analogs of the latter betaine suggest that metal species of intermediate ‘softness’ prefer endocyclic N1 binding over exocyclic O6 to a larger extent than they prefer endocyclic N3 binding over exocyclic O2 binding in cytosine derivatives 2-Dimethylamino-9-methylhypoxanthine I (R,R¹ = Me; R² = Me) was prepared from 5-amino-4,6-dihydroxy-2-dimethylaminopyrimidine II (R³ = NH₂, R⁴ = OH, R⁵ = NMe₂) by addition of MeNCS, ring closure with HCL, and Raney nickel desulfurization. I (R,R¹ = H, Et; R² = Pr) were prepared from II (R³ = NO₂, R⁴ = NH₂, R⁵ = SMe) by treatment with Me₂NH, EtNH₂, or Et₂NH followed by cycloadditions with Na₂S₂O₄, HCO₂H₂ and CHCONH₂ alkylation with alkyl halides, and deamination with HNO₂. I were methylated to give the corresponding hypoxanthinium betaines III.

Inorganica Chimica Acta 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 C6H17NO3Si, Product Details of C6H9N3O2.

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

Proba, Zbigniew published the artcileConformation of the dimethylamino group in benzene, pyridine, pyrimidine, and cytosine derivatives. Carbon-13 chemical shift studies of ortho-methyl substitution effects, Synthetic Route of 31401-45-3, the publication is Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) (1978), 1119-23, database is CAplus.

The ¹³C NMR spectra of C₆H₆ derivatives I (R = H, Me), pyrimidines II (RR¹ = bond, R² = H; R³ = H, Me, R⁴ = NMe₂; R³ = NMe₂, R⁴ = H, Me), oxopyrimidines II (R = Me, R¹R² = O, R³ = NMe₂, R⁴ = H, Me) and pyridines III (R = H, Me) are reported. Anal. of the chem. shifts of C-Me and amino N-Me C atoms as well as C-Me and C-NMe₂ ring-C atoms showed a progressive twist of the NMe₂ group in hindered derivatives from a planar conformation in the 2-oxopyrimidine compounds to the most twisted one in I (R = H).

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C6H9N3, Synthetic Route of 31401-45-3.

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

Smagowicz, J. published the artcileThe phosphorescence of hindered aminopyrimidines, Application of N,N-Dimethylpyrimidin-4-amine, the publication is Journal of Luminescence (1976), 14(1), 9-18, database is CAplus.

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 ∼10 times stronger than that of the lowest 1(l,aπ*).

Journal of Luminescence published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C22H18Cl2N2, Application of N,N-Dimethylpyrimidin-4-amine.

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

Pienko, Tomasz published the artcileConformational Dynamics of Cyanocobalamin and Its Conjugates with Peptide Nucleic Acids, Safety of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, the publication is Journal of Physical Chemistry B (2017), 121(14), 2968-2979, database is CAplus and MEDLINE.

Vitamin B₁₂ also called cobalamin (Cbl) is an important enzymic co-factor taken up by mammalian and also by many bacterial cells. Peptide nucleic acid (PNA) is a synthetic DNA analog that has the ability to bind in a complementary manner to natural nucleic acids. Provided that PNA is efficiently delivered to cells, it could act as a steric blocker of functional DNA or RNA and regulate gene expression at the level of transcription or translation. Recently, Cbl has been examined as a transporter of various mols. to cells. Also, PNA if covalently linked with Cbl, can be delivered to bacterial cells but it is crucial to verify that Cbl does not change the desired PNA biol. properties. We have analyzed the structure and conformational dynamics of conjugates of Cbl with a PNA monomer and oligomer. We synthesized a cyanocobalamin derivative with a PNA monomer C connected via the triazole linker and determined its NMR spectra. Using microsecond-long mol. dynamics simulations, we examined the internal dynamics of cyanocobalamin-C, its conjugate with a 14-mer PNA, and free PNA. The results suggest that all compounds acquire rather compact structures but the PNA oligomer conformations vary. For the Cbl-C conjugate the cross-peaks from the ROESY spectrum corroborated with the clusters from mol. dynamics trajectories. Within PNA the dominant interaction is stacking but the stacking bases are not necessarily neighboring in the PNA sequence. More bases stack in free PNA than in PNA of the conjugate but stacking is less stable in free PNA. PNA in the conjugate is slightly more exposed to solvent. Overall, cyanocobalamin attached to a PNA oligomer increases the flexibility of PNA in a way that could be beneficial for its hybridization with natural nucleic acid oligomers.

Journal of Physical Chemistry B 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, Safety of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid.

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