Day: November 25, 2022

Li, Nan published the artcileCopper-Free Sonogashira Cross-Coupling for Functionalization of Alkyne-Encoded Proteins in Aqueous Medium and in Bacterial Cells, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Journal of the American Chemical Society (2011), 133(39), 15316-15319, database is CAplus and MEDLINE.

Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction (“click chem.”), have provided chem. tools to study biomol. dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biol. applications has not been reported. In this work, the authors report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chem.

Journal of the American Chemical Society 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, Safety of 2-Amino-4,6-dichloropyrimidine.

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

Malik, Shipra published the artcileNext generation miRNA inhibition using short anti-seed PNAs encapsulated in PLGA nanoparticles, Application In Synthesis of 186046-81-1, the publication is Journal of Controlled Release (2020), 406-419, database is CAplus and MEDLINE.

Selective inhibition of microRNAs (miRNAs) offers a new avenue for cancer therapeutics. While most of the current anti-miRNA (antimiR) reagents target full length miRNAs, here we investigate novel nanoparticle-delivered short PNA probes containing cationic domains targeting the seed region of the miRNA for effective antimiR therapy. For proof of concept, we tested PNAs targeting miRNA-155 and employed poly(lactic-co-glycolic acid) (PLGA)-based nanoparticle formulation for delivery. A comprehensive evaluation of PLGA nanoparticles (NPs) containing short PNA probes showed significantly superior loading, release profile, and uniform size distribution, compared to conventional non-cationic PNA probes. Confocal microscopy and flow cytometry analyses showed efficient transfection efficiency and uniform distribution of PLGA NPs containing short PNA probes in the cytoplasm. Functional anal. also confirmed efficient miRNA-155 inhibition including an effect on its downstream target proteins. Further, reduced tumor growth was observed after systemic delivery of PLGA nanoparticles containing short PNA probes in vivo in a xenograft mouse model following inhibition of miR-155. There was no evidence of acute or chronic toxicity associated with systemic delivery of PLGA NPs containing short PNA probes in the mice. Overall, in this paper we present a novel antimiR strategy based on PLGA nanoparticle delivered short PNA probes for potential cancer therapy.

Journal of Controlled Release 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, Application In Synthesis of 186046-81-1.

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

Malik, Shipra published the artcileNext generation miRNA inhibition using short anti-seed PNAs encapsulated in PLGA nanoparticles, HPLC of Formula: 169396-92-3, the publication is Journal of Controlled Release (2020), 406-419, database is CAplus and MEDLINE.

Selective inhibition of microRNAs (miRNAs) offers a new avenue for cancer therapeutics. While most of the current anti-miRNA (antimiR) reagents target full length miRNAs, here we investigate novel nanoparticle-delivered short PNA probes containing cationic domains targeting the seed region of the miRNA for effective antimiR therapy. For proof of concept, we tested PNAs targeting miRNA-155 and employed poly(lactic-co-glycolic acid) (PLGA)-based nanoparticle formulation for delivery. A comprehensive evaluation of PLGA nanoparticles (NPs) containing short PNA probes showed significantly superior loading, release profile, and uniform size distribution, compared to conventional non-cationic PNA probes. Confocal microscopy and flow cytometry analyses showed efficient transfection efficiency and uniform distribution of PLGA NPs containing short PNA probes in the cytoplasm. Functional anal. also confirmed efficient miRNA-155 inhibition including an effect on its downstream target proteins. Further, reduced tumor growth was observed after systemic delivery of PLGA nanoparticles containing short PNA probes in vivo in a xenograft mouse model following inhibition of miR-155. There was no evidence of acute or chronic toxicity associated with systemic delivery of PLGA NPs containing short PNA probes in the mice. Overall, in this paper we present a novel antimiR strategy based on PLGA nanoparticle delivered short PNA probes for potential cancer therapy.

Journal of Controlled Release 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

Liu, Li-Han published the artcileSelf-Assembly of Hybridized Peptide Nucleic Acid Amphiphiles, HPLC of Formula: 186046-81-1, the publication is ACS Macro Letters (2014), 3(5), 467-471, database is CAplus and MEDLINE.

In this report, a series of peptide nucleic acid amphiphiles (PNAAs) with hybridization properties were designed and synthesized. Driven by hydrophobic interaction, the hybridized PNAAs can form uniform micelles, the base stacking interaction from PNA segments further stabilized the micelles. The effects of hydrophobic alkyl chain length, structure of hydrophilic peptides, concentration, and pH on the self-assembly behavior of partly complementing PNAA duplexes were explored.

ACS Macro Letters 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

Liu, Li-Han published the artcileSelf-Assembly of Hybridized Peptide Nucleic Acid Amphiphiles, Synthetic Route of 169396-92-3, the publication is ACS Macro Letters (2014), 3(5), 467-471, database is CAplus and MEDLINE.

In this report, a series of peptide nucleic acid amphiphiles (PNAAs) with hybridization properties were designed and synthesized. Driven by hydrophobic interaction, the hybridized PNAAs can form uniform micelles, the base stacking interaction from PNA segments further stabilized the micelles. The effects of hydrophobic alkyl chain length, structure of hydrophilic peptides, concentration, and pH on the self-assembly behavior of partly complementing PNAA duplexes were explored.

ACS Macro 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 C26H26N4O7, Synthetic Route of 169396-92-3.

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

Peng, Cheng published the artcileInhibitor development of MTH1 via high-throughput screening with fragment based library and MTH1 substrate binding cavity, Product Details of C4H3Cl2N3, the publication is Bioorganic Chemistry (2021), 104813, database is CAplus and MEDLINE.

MutT Homolog 1 (MTH1) has been proven to hydrolyze oxidized nucleotide triphosphates during DNA repair. It can prevent the incorporation of wrong nucleotides during DNA replication and mitigate cell apoptosis. In a cancer cell, abundant reactive oxygen species can lead to substantial DNA damage and DNA mutations by base-pairing mismatch. MTH1 could eliminate oxidized dNTP and prevent cancer cells from entering cell death. Therefore, inhibition of MTH1 activity is considered to be an anti-cancer therapeutic target. In this study, high-throughput screening techniques were combined with a fragment-based library containing 2,313 compounds, which were used to screen for lead compounds with MTH1 inhibitor activity. Four compounds with MTH1 inhibitor ability were selected, and compound MI0639 was found to have the highest effective inhibition. To discover the selectivity and specificity of this action, several derivatives based on the MTH1 and MI0639 complex structure were synthesized. We compared 14 complex structures of MTH1 and the various compounds in combination with enzymic inhibition and thermodn. anal. Nanomolar-range IC50 inhibition abilities by enzyme kinetics and Kd values by thermodn. anal. were obtained for two compounds, named MI1020 and MI1024. Based on structural information and compound optimization, we aim to provide a strategy for the development of MTH1 inhibitors with high selectivity and specificity.

Bioorganic 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, Product Details of C4H3Cl2N3.

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

Yang, Qiang published the artcileDevelopment of a Scalable Process for the Insecticidal Candidate Tyclopyrazoflor. Part 2. Fit-for-Purpose Optimization of the Route to Tyclopyrazoflor Featuring [3 + 2] Cyclization of 3-Hydrazinopyridine·2HCl and Methyl Acrylate, Synthetic Route of 31401-45-3, the publication is Organic Process Research & Development (2019), 23(10), 2133-2141, database is CAplus.

Optimization of the route to the sap-feeding insecticidal candidate tyclopyrazoflor (I) featuring [3 + 2] cyclization of 3-hydrazinopyridine·2HCl and Me acrylate is described. The key impurities in the [3 + 2] cyclization were identified and successfully controlled after optimization. The hazards associated with oxidation of an intermediate pyrazolidin-3-one using the incompatible combination of potassium persulfate and N,N-dimethylformamide (DMF) were avoided by using potassium ferricyanide in the presence of potassium hydroxide in water. The two elimination impurities in the ethylation step to produce tyclopyrazoflor were successfully minimized using Et iodide in the presence of cesium carbonate in DMF at 0 °C. The overall yield for this seven-step synthesis of tyclopyrazoflor was improved from 10% to 41% after the optimization detailed herein.

Organic Process Research & Development 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 C9H7NO3, Synthetic Route of 31401-45-3.

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

Zengeya, Thomas published the artcilePNA containing isocytidine nucleobase: Synthesis and recognition of double helical RNA, 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 Bioorganic & Medicinal Chemistry Letters (2011), 21(7), 2121-2124, database is CAplus and MEDLINE.

Peptide nucleic acid (PNA1) containing a 5-methylisocytidine (iC) nucleobase has been synthesized. Triple helix formation between PNA1 and RNA hairpins having variable base pairs interacting with iC was studied using isothermal titration calorimetry. The iC nucleobase recognized the proposed target, C-G inversion in polypurine tract of RNA, with slightly higher affinity than the natural nucleobases, though the sequence selectivity of recognition was low. Compared to non-modified PNA, PNA1 had lower affinity for its RNA target.

Bioorganic & Medicinal Chemistry Letters 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 C34H33ClN6O7, 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

Zengeya, Thomas published the artcilePNA containing isocytidine nucleobase: Synthesis and recognition of double helical RNA, SDS of cas: 169396-92-3, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(7), 2121-2124, database is CAplus and MEDLINE.

Peptide nucleic acid (PNA1) containing a 5-methylisocytidine (iC) nucleobase has been synthesized. Triple helix formation between PNA1 and RNA hairpins having variable base pairs interacting with iC was studied using isothermal titration calorimetry. The iC nucleobase recognized the proposed target, C-G inversion in polypurine tract of RNA, with slightly higher affinity than the natural nucleobases, though the sequence selectivity of recognition was low. Compared to non-modified PNA, PNA1 had lower affinity for its RNA target.

Bioorganic & Medicinal Chemistry 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 C28H29NO4, SDS of cas: 169396-92-3.

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

Huang, Luyi published the artcileDiscovery of Pyrrolo[3,2-d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain, Category: pyrimidines, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4526-4542, database is CAplus and MEDLINE.

Herein, we report the discovery of a series of new P300/CBP-associated factor (PCAF) bromodomain (BRD) inhibitors, which were obtained through a hit discovery process and subsequent structure-based optimization and structure-activity relationship analyses toward a retrieved hit compound (12). Among these inhibitors, (R,R)-36n is the most potent one with an IC₅₀ of 7 nM in homogeneous time-resolved fluorescence assay and a K_D of 78 nM in isothermal titration calorimetry assay. This compound also exhibited activity against GCN5 and FALZ, but weak or no activity against other 29 BRD proteins and 422 kinases, indicating considerable selectivity. X-ray cocrystal structure anal. revealed the mol. interaction mode and the precise stereochem. required for bioactivity. Cellular activity, preliminary RNA-seq anal., and pharmacokinetic properties were also examined for this compound Collectively, this study provides a versatile tool mol. to explore mol. mechanisms of PCAF BRD regulation and also offers a new lead compound for drug discovery targeting PCAF.

Journal of Medicinal Chemistry published new progress about 2351929-82-1. 2351929-82-1 belongs to pyrimidines, auxiliary class Pyrroles, name is 2-Chloro-3-methyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, and the molecular formula is C7H6ClN3O, Category: pyrimidines.

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