Month: November 2022

Li, Chengxi published the artcileAutomated Flow Synthesis of Peptide-PNA Conjugates, HPLC of Formula: 186046-81-1, the publication is ACS Central Science (2022), 8(2), 205-213, database is CAplus and MEDLINE.

Antisense peptide nucleic acids (PNAs) have yet to translate to the clinic because of poor cellular uptake, limited solubility, and rapid elimination. Cell-penetrating peptides (CPPs) covalently attached to PNAs may facilitate clin. development by improving uptake into cells. We report an efficient technol. that utilizes a fully automated fast-flow instrument to manufacture CPP-conjugated PNAs (PPNAs) in a single shot. The machine is rapid, with each amide bond being formed in 10 s. Anti-IVS2-654 PPNA synthesized with this instrument presented threefold activity compared to transfected PNA in a splice-correction assay. We demonstrated the utility of this approach by chem. synthesizing eight anti-SARS-CoV-2 PPNAs in 1 day. A PPNA targeting the 5′ untranslated region of SARS-CoV-2 genomic RNA reduced the viral titer by over 95% in a live virus infection assay (IC₅₀ = 0.8 μM). Our technol. can deliver PPNA candidates to further investigate their potential as antiviral agents.

ACS Central 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, HPLC of Formula: 186046-81-1.

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

Li, Chengxi published the artcileAutomated Flow Synthesis of Peptide-PNA Conjugates, HPLC of Formula: 169396-92-3, the publication is ACS Central Science (2022), 8(2), 205-213, database is CAplus and MEDLINE.

Antisense peptide nucleic acids (PNAs) have yet to translate to the clinic because of poor cellular uptake, limited solubility, and rapid elimination. Cell-penetrating peptides (CPPs) covalently attached to PNAs may facilitate clin. development by improving uptake into cells. We report an efficient technol. that utilizes a fully automated fast-flow instrument to manufacture CPP-conjugated PNAs (PPNAs) in a single shot. The machine is rapid, with each amide bond being formed in 10 s. Anti-IVS2-654 PPNA synthesized with this instrument presented threefold activity compared to transfected PNA in a splice-correction assay. We demonstrated the utility of this approach by chem. synthesizing eight anti-SARS-CoV-2 PPNAs in 1 day. A PPNA targeting the 5′ untranslated region of SARS-CoV-2 genomic RNA reduced the viral titer by over 95% in a live virus infection assay (IC₅₀ = 0.8 μM). Our technol. can deliver PPNA candidates to further investigate their potential as antiviral agents.

ACS Central Science 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 C26H26N4O7, HPLC of Formula: 169396-92-3.

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

Rapp, Magdalena published the artcileReactions of trimethylsilyl fluorosulfonyldifluoroacetate with purine and pyrimidine nucleosides, Application of 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Journal of Fluorine Chemistry (2009), 130(3), 321-328, database is CAplus and MEDLINE.

Difluorocarbene, generated from trimethylsilyl fluorosulfonyldifluoroacetate (TFDA), reacts with the uridine and adenosine substrates preferentially at the enolizable amide moiety of the uracil ring and the 6-amino group of the purine ring. 2′,3′-Di-O-benzoyl-3′-deoxy-3′-methyleneuridine reacts with TFDA to produce 4-O-difluoromethyl product derived from an insertion of difluorocarbene into the 4-hydroxyl group of the enolizable uracil ring. Reaction of the difluorocarbene with the adenosine substrates having the unprotected 6-amino group in the purine ring produced the 6-N-difluoromethyl derivative, while reaction with 6-N-benzoyl protected adenosine analogs gave the difluoromethyl ether product derived from the insertion of difluorocarbene into the enol form of the 6-benzamido group. Treatment of the 6-N-phthaloyl protected adenosine analogs with TFDA resulted in the unexpected one-pot conversion of the imidazole ring of the purine into the corresponding N-difluoromethylthiourea derivatives Treatment of the suitably protected pyrimidine and purine nucleosides bearing an exo-methylene group at carbons 2′, 3′ or 4′ of the sugar rings with TFDA afforded the corresponding spiro-difluorocyclopropyl analogs but in low yields.

Journal of Fluorine Chemistry 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, Application of 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Tang, Qi published the artcileCharacterization of Byproducts from Chemical Syntheses of Oligonucleotides Containing 1-Methyladenine and 3-Methylcytosine, Category: pyrimidines, the publication is ACS Omega (2017), 2(11), 8205-8212, database is CAplus and MEDLINE.

Oligonucleotides serve as important tools for biol., chem., and medical research. The preparation of oligonucleotides through automated solid-phase synthesis is well established. However, identification of byproducts generated from DNA synthesis, especially from oligonucleotides containing site-specific modifications, is sometimes challenging. Typical HPLC, Mass Spectrometry (MS), and gel electrophoresis methods alone are not sufficient for characterizing unexpected byproducts, especially for those having identical or very similar mol. weight (MW) to the products. The authors used a rigorous quality control procedure to characterize byproducts generated during oligonucleotide syntheses: (1) purify oligonucleotide by different HPLC systems; (2) determine the exact MW by high resolution MS; (3) locate modification position by MS/MS or exonuclease digestion with MALDI-TOF anal.; and (4) conduct, where applicable, enzymic assays. The authors applied these steps to characterize byproducts in the syntheses of oligonucleotides containing important Me DNA adducts 1-methyladenine (m1A) and 3-methylcytosine (m3C). In m1A synthesis, the authors differentiated a regioisomeric byproduct 6-methyladenine, which possesses identical MW to m1A. As for m3C, the authors identified a deamination byproduct 3-methyluracil, which is only 1 Da greater than m3C in the ∼ 4900 Da context. The detection of these byproducts would be very challenging if the abovementioned procedure were not adopted.

ACS Omega 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 C14H12N2S, Category: pyrimidines.

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

Scheibe, Christian published the artcileDNA-programmed spatial screening of carbohydrate-lectin interactions, Name: 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 Chemical Science (2011), 2(4), 770-775, database is CAplus.

A wide range of multivalent scaffolds was assembled by using only five different PNA oligomers and various DNA templates. The flexibility of the PNA-DNA duplexes could be increased by introducing nick-sites and partially unpaired regions, as confirmed by MD simulations. The self-organized glyco-assemblies were used in a spatial screening of accessible carbohydrate binding sites in the Erythrina cristagalli lectin (ECL). This systematic investigation revealed a distance dependence which is in agreement with the crystal structure anal.

Chemical 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, Name: 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

Scheibe, Christian published the artcileDNA-programmed spatial screening of carbohydrate-lectin interactions, Computed Properties of 169396-92-3, the publication is Chemical Science (2011), 2(4), 770-775, database is CAplus.

A wide range of multivalent scaffolds was assembled by using only five different PNA oligomers and various DNA templates. The flexibility of the PNA-DNA duplexes could be increased by introducing nick-sites and partially unpaired regions, as confirmed by MD simulations. The self-organized glyco-assemblies were used in a spatial screening of accessible carbohydrate binding sites in the Erythrina cristagalli lectin (ECL). This systematic investigation revealed a distance dependence which is in agreement with the crystal structure anal.

Chemical Science 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 C26H26N4O7, Computed Properties of 169396-92-3.

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

Nyeki, A. published the artcileNAT2 and CYP1A2 phenotyping with caffeine: head-to-head comparison of AFMU vs. AAMU in the urine metabolite ratios, HPLC of Formula: 608-34-4, the publication is British Journal of Clinical Pharmacology (2003), 55(1), 62-67, database is CAplus and MEDLINE.

Aims. (i) To compare the phenotyping of healthy subjects for NAT2 (N-acetyltransferase) and CYP1A2 activities with caffeine, by the simultaneous assay of the urinary metabolites AFMU and AAMU, and (ii) to ascertain whether NAT2 and CYP1A2 phenotyping is influenced by the use of AFMU or AAMU in the metabolite ratio. Methods. Thirty-five healthy subjects (16 men, 19 women) participated to the study. Caffeine metabolite concentrations were measured in urine collected 8 h after 2.5 mg kg^-1 caffeine intake using a new validated h.p.l.c. method. The metabolite ratios AFMU/1X, AFMU/(AFMU+1X+1U), AAMU/1X, AAMU/(AAMU+1X+1 U), and (AFMU+1U+1X)/17U, (AAMU+1U+1X)/17U were determined as indexes of NAT2 and CYP1A2 activity, resp. Results. Slow and rapid acetylators were similarly identified using the four NAT2 metabolite ratios in 139 out of 1.40 measurements. An appreciable amount of AAMU was present in urine that was immediately acidified and analyzed. Consequently, the ratio using AFMU was lower than that using total AAMU following transformation of AFMU in basic conditions. The proportion of AFMU in urine analyzed immediately expressed as AFMU/(AFMU+AAMU) ratio did not correlate with urine pH, but was a function of the acetylation phenotype, with a low intergroup variability (64±3% and 32±5%, for rapid and slow acetylators, resp.; P < 0.00001, ANOVA). Regarding CYP1A2 activity, a good correlation (r = 0.99) was observed between the metabolite ratios calculated from AFMU and AAMU, although the ratios calculated from AFMU were proportionately and systematically lower (P < 0.00001, paired t-test, slope 1.2). Conclusions. This study demonstrates that both AFMU and AAMU can be used for NAT2 and CYP1A2 metabolite ratio determinations The reported conversion of AFMU into AAMU is unlikely to explain the large amount of AAMU in urine that was acidified and analyzed immediately after voiding. The results suggest that AAMU is formed not solely through a nonenzymic hydrolysis in urine, but in vivo by a NAT2 phenotype-dependent pathway.

British Journal of Clinical Pharmacology 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, HPLC of Formula: 608-34-4.

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

Mahe, Yann published the artcileA minoxidil-related compound lacking a C6 substitution still exhibits strong anti-lysyl hydroxylase activity in vitro, Related Products of pyrimidines, the publication is Skin Pharmacology (1996), 9(3), 177-183, database is CAplus.

It has been previously reported that minoxidil inhibits the activity of lysyl hydroxylase (LH), an enzyme which catalyzes the formation of hydroxylysine, which is necessary for proper maturation of collagen at the transcriptional and enzymic levels. Using the reverse transcriptase-polymerase chain reaction, we confirmed that this inhibition occurred at least at the transcriptional level. Furthermore, we took advantage of this sensitive and rapid method to perform a quant. structure activity relation study using several compounds structurally related to minoxidil. We found that when the C6 of the pyrimidinyl moiety was substituted, it had to be by a tertiary nitrogen, i.e. an N-piperidin ring for the inhibition of LH mRNA synthesis to be observed Surprisingly, however, we found that 2,4-diamino-pyrimidin-3-oxide, a new compound lacking an organic moiety para to the nitroxide oxygen, also retained a high inhibitory effect on LH mRNA expression, comparable to that of minoxidil. We thus conclude that the presence of a substituent para to the nitroxide oxygen is dispensable for inhibition of LH mRNA to be observed in vitro. This brings new insights into the design of therapeutic agents useful in any condition where an overproduction of mature collagen is unwanted, i.e. accelerated wound healing, keloids and localized scleroderma.

Skin Pharmacology published new progress about 74638-76-9. 74638-76-9 belongs to pyrimidines, auxiliary class Pyrimidine, name is 2,4-Diaminopyrimidine-3-oxide, and the molecular formula is C4H6N4O, Related Products of pyrimidines.

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

Panchaud, Philippe published the artcileDiscovery and Optimization of Isoquinoline Ethyl Ureas as Antibacterial Agents, Computed Properties of 1187931-22-1, the publication is Journal of Medicinal Chemistry (2017), 60(9), 3755-3775, database is CAplus and MEDLINE.

Our strategy to combat resistant bacteria consisted of targeting the GyrB/ParE ATP-binding sites located on bacterial DNA gyrase and topoisomerase IV and not utilized by marketed antibiotics. Screening around the minimal Et urea binding motif led to the identification of isoquinoline Et urea 13 as a promising starting point for fragment evolution. The optimization was guided by structure-based design and focused on antibacterial activity in vitro and in vivo, culminating in the discovery of unprecedented substituents able to interact with conserved residues within the ATP-binding site. A detailed characterization of the lead compound highlighted the potential for treatment of the problematic fluoroquinolone-resistant MRSA, VRE, and S. pneumoniae, and the possibility to offer patients an i.v.-to-oral switch therapy was supported by the identification of a suitable prodrug concept. Eventually, hERG K-channel block was identified as the main limitation of this chem. series, and efforts toward its minimization are reported.

Journal of Medicinal Chemistry published new progress about 1187931-22-1. 1187931-22-1 belongs to pyrimidines, auxiliary class Pyrimidine,Bromide,Salt, name is 4-Bromopyrimidine hydrobromide, and the molecular formula is C4H4Br2N2, Computed Properties of 1187931-22-1.

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

Riand, J. published the artcileMass spectrometry. Induced fragmentation by electron impact of amino and dimethylaminopyrimidines, Recommanded Product: N,N-Dimethylpyrimidin-4-amine, the publication is Journal of Heterocyclic Chemistry (1983), 20(5), 1187-90, database is CAplus.

Fragmentation patterns for I (R = R² = H, R¹ = NH₂; R = R¹ = NH₂, R² = H; R = R¹ = R² = NH₂; R= Me₂N, R¹ = R² = H; R = R² = H, R¹ = Me₂N; R = R¹ = Me₂N, R² = H; R = R¹ = R² = Me₂N) were determined and discussed.

Journal of Heterocyclic Chemistry 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, Recommanded Product: N,N-Dimethylpyrimidin-4-amine.

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