Day: December 6, 2022

Dumas, Anaelle published the artcileSelf-Liganded Suzuki-Miyaura Coupling for Site-Selective Protein PEGylation, Application of 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is Angewandte Chemie, International Edition (2013), 52(14), 3916-3921, database is CAplus and MEDLINE.

PEG-boronic acids, in the presence of simple Pd sources, are capable of acting as direct and effective Suzuki reagents in 70-98% yield. When combined with non-natural amino acids, they allow efficient and direct, site-selective PEGylation of proteins at predetermined positions under biol. compatible conditions without the need for exogenous ligands.

Angewandte Chemie, International Edition 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, Application of 2-(Dimethylamino)pyrimidine-4,6-diol.

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

Zhang, Chao published the artcileRAF inhibitors that evade paradoxical MAPK pathway activation, Application In Synthesis of 1375301-91-9, the publication is Nature (London, United Kingdom) (2015), 526(7574), 583-586, database is CAplus and MEDLINE.

Oncogenic activation of BRAF fuels cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase (MAPK) pathway signalling. Accordingly, RAF inhibitors have brought substantially improved personalized treatment of metastatic melanoma. However, these targeted agents have also revealed an unexpected consequence: stimulated growth of certain cancers. Structurally diverse ATP-competitive RAF inhibitors can either inhibit or paradoxically activate the MAPK pathway, depending whether activation is by BRAF mutation or by an upstream event, such as RAS mutation or receptor tyrosine kinase activation. Here we have identified next-generation RAF inhibitors (dubbed ‘paradox breakers’) that suppress mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation. In cells that express the same HRAS mutation prevalent in squamous tumors from patients treated with RAF inhibitors, the first-generation RAF inhibitor vemurafenib stimulated in vitro and in vivo growth and induced expression of MAPK pathway response genes; by contrast the paradox breakers PLX7904 and PLX8394 had no effect. Paradox breakers also overcame several known mechanisms of resistance to first-generation RAF inhibitors. Dissociating MAPK pathway inhibition from paradoxical activation might yield both improved safety and more durable efficacy than first-generation RAF inhibitors, a concept currently undergoing human clin. evaluation with PLX8394.

Nature (London, United Kingdom) published new progress about 1375301-91-9. 1375301-91-9 belongs to pyrimidines, auxiliary class Pyrimidine,Boronic acid and ester,Boronate Esters,Boronic acid and ester, name is 2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, and the molecular formula is C10H9NO, Application In Synthesis of 1375301-91-9.

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

Gasser, Gilles published the artcileTowards the Preparation of Novel Re/^99mTc Tricarbonyl-Containing Peptide Nucleic Acid Bioconjugates, COA of Formula: C39H35N5O8, the publication is Australian Journal of Chemistry (2011), 64(3), 265-272, database is CAplus.

A novel azido derivative of the di-(2-picolyl)amide (Dpam) ligand, namely 3-azido-N,N-bis-pyridin-2-ylmethylpropionamide (3), was prepared from 3-bromo-N,N-bis(pyridin-2-ylmethyl)propanamide (2) with an excess of sodium azide in DMSO. 3 Was then reacted, by Cu(I)-catalyzed [3+2] cycloaddition (often referred to as click chem.), with the previously reported alkyne-containing peptide nucleic acid (PNA) monomer Fmoc-1-OBu-t to give the Dpam-containing PNA monomer (Fmoc-4-OBu-t) in 44% yield. It was also demonstrated that 3 could be reacted by click chem., on the solid phase, to an alkyne-containing PNA oligomer (alkyne-PNA) to yield Dpam-PNA. The attempts to complex Dpam-PNA with [NEt₄]₂[ReBr₃(CO)₃] and [^99mTc(CO)₃(H₂O)₃]⁺ are also discussed in detail.

Australian Journal of Chemistry 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, COA of Formula: C39H35N5O8.

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

Gasser, Gilles published the artcileTowards the Preparation of Novel Re/^99mTc Tricarbonyl-Containing Peptide Nucleic Acid Bioconjugates, Category: pyrimidines, the publication is Australian Journal of Chemistry (2011), 64(3), 265-272, database is CAplus.

A novel azido derivative of the di-(2-picolyl)amide (Dpam) ligand, namely 3-azido-N,N-bis-pyridin-2-ylmethylpropionamide (3), was prepared from 3-bromo-N,N-bis(pyridin-2-ylmethyl)propanamide (2) with an excess of sodium azide in DMSO. 3 Was then reacted, by Cu(I)-catalyzed [3+2] cycloaddition (often referred to as click chem.), with the previously reported alkyne-containing peptide nucleic acid (PNA) monomer Fmoc-1-OBu-t to give the Dpam-containing PNA monomer (Fmoc-4-OBu-t) in 44% yield. It was also demonstrated that 3 could be reacted by click chem., on the solid phase, to an alkyne-containing PNA oligomer (alkyne-PNA) to yield Dpam-PNA. The attempts to complex Dpam-PNA with [NEt₄]₂[ReBr₃(CO)₃] and [^99mTc(CO)₃(H₂O)₃]⁺ are also discussed in detail.

Australian Journal of 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 C26H26N4O7, Category: pyrimidines.

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

Henderson, Scott H. published the artcileDiscovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors, Related Products of pyrimidines, the publication is Journal of Medicinal Chemistry (2021), 64(15), 11709-11728, database is CAplus and MEDLINE.

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) regulates the proliferation and differentiation of neuronal progenitor cells during brain development. Consequently, DYRK1A has attracted interest as a target for the treatment of neurodegenerative diseases, including Alzheimer′s disease (AD) and Down′s syndrome. Recently, the inhibition of DYRK1A has been investigated as a potential treatment for diabetes, while DYRK1A′s role as a mediator in the cell cycle has garnered interest in oncol. indications. Structure-activity relationship (SAR) anal. in combination with high-resolution X-ray crystallog. leads to a series of pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochem. properties, and a high degree of selectivity over the kinome. Compound 11 (I) exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the treatment of diseases linked to DYRK1A function.

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, Related Products of pyrimidines.

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

Dettin, Monica published the artcileSynthesis and chromatography-free purification of PNA-PEO conjugates for the functionalisation of gold sensors, Application In Synthesis of 186046-81-1, the publication is Molecules (2012), 11026-11045, database is CAplus and MEDLINE.

Peptide Nucleic Acids (PNAs) linked to high mol. weight (MW) poly(ethylene oxide) (PEO) derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR)-based DNA sensing. However their use is hampered by the difficulty to obtain them through a convenient and economical route. In this work we compared three synthetic strategies to obtain PNA-high MW PEO conjugates composed of (a) a 15-mer PNA sequence as the probe complementary to genomic DNA of Mycobacterium tuberculosis, (b) a PEO moiety (2 or 5 KDa MW) and (c) a terminal trityl-protected thiol necessary (after acidic deprotection) for grafting to gold surfaces. The 15-mer PNA was obtained by solid-phase synthesis. Its amino terminal group was later condensed to bi-functional PEO derivatives (2 and 5 KDa MW) carrying a Trt-cysteine at one end and a carboxyl group at the other end. The reaction was carried out either in solution, using HATU or PyOxim as coupling agents or through the solid-phase approach, with 49.6%, 100% and 5.2% yield, resp. A differential solvent extraction strategy for product purification without the need for chromatog. is described. The ability of the 5 KDa PEO conjugate to function as a probe for complementary DNA detection was demonstrated using a Grating-Coupling Surface Plasmon Resonance (GC-SPR) system. The optimized PEO conjugation and purification protocols are economical and simple enough to be reproduced also within laboratories that are not highly equipped for chem. synthesis.

Molecules 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

Dettin, Monica published the artcileSynthesis and chromatography-free purification of PNA-PEO conjugates for the functionalisation of gold sensors, Related Products of pyrimidines, the publication is Molecules (2012), 11026-11045, database is CAplus and MEDLINE.

Peptide Nucleic Acids (PNAs) linked to high mol. weight (MW) poly(ethylene oxide) (PEO) derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR)-based DNA sensing. However their use is hampered by the difficulty to obtain them through a convenient and economical route. In this work we compared three synthetic strategies to obtain PNA-high MW PEO conjugates composed of (a) a 15-mer PNA sequence as the probe complementary to genomic DNA of Mycobacterium tuberculosis, (b) a PEO moiety (2 or 5 KDa MW) and (c) a terminal trityl-protected thiol necessary (after acidic deprotection) for grafting to gold surfaces. The 15-mer PNA was obtained by solid-phase synthesis. Its amino terminal group was later condensed to bi-functional PEO derivatives (2 and 5 KDa MW) carrying a Trt-cysteine at one end and a carboxyl group at the other end. The reaction was carried out either in solution, using HATU or PyOxim as coupling agents or through the solid-phase approach, with 49.6%, 100% and 5.2% yield, resp. A differential solvent extraction strategy for product purification without the need for chromatog. is described. The ability of the 5 KDa PEO conjugate to function as a probe for complementary DNA detection was demonstrated using a Grating-Coupling Surface Plasmon Resonance (GC-SPR) system. The optimized PEO conjugation and purification protocols are economical and simple enough to be reproduced also within laboratories that are not highly equipped for chem. synthesis.

Molecules 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, Related Products of pyrimidines.

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

Fung, B. M. published the artcileDynamic NMR in liquid-crystal solutions. Hindered rotation in 4-(dimethylamino)pyrimidine, Category: pyrimidines, the publication is Journal of the American Chemical Society (1984), 106(24), 7301-4, database is CAplus.

The hindered rotation of the dimethylamino group in 4-(dimethylamino)pyrimidine in a liquid-crystal solution (Merck ZLI 2142) was studied from 232 to 263 K by natural-abundance carbon-13 NMR. The enthalpies of activation were 53, 35, and 52 kJ mol^-1 in the liquid crystal, CD₂Cl₂, and CD₃OD, resp. The ordering forces of the liquid-crystal solvent may favor the planar ground state of the solute more than the bulkier transition state, causing the barrier of rotation to be unusually high.

Journal of the American Chemical Society 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, Category: pyrimidines.

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

Brown, D. J. published the artcilePyrimidines. I. Spectroscopic studies, Related Products of pyrimidines, the publication is Journal of the Chemical Society (1953), 331-7, database is CAplus.

Crude 2-chloropyrimidine (I) (2 g.) and NaOMe (from 0.5 g. Na and 25 ml. MeOH) refluxed 0.5 hr., cooled, saturated with CO₂, filtered, the filtrate concentrated in vacuo, the residue extracted with 40 ml. Et₂O, and the dried extract concentrated and distilled gave 0.83 g. 2-methoxypyrimidine (II), colorless liquid, b₁₅ 70-1°, n²⁰_D 1.5060. II (2.4 g.) and 20 ml. 15% Me₂NH-MeOH heated 1 hr. at 120°, NaOMe (from 0.4 g. Na in 20 ml. MeOH) added, and the mixture worked up as above (but without refluxing) gave 1.2 g. 2-(dimethylamino)pyrimidine (III), colorless hygroscopic liquid, b₁₇ 78-81°, n²²_D 1.5438. II and MeNH₂-EtOH similarly gave 2-(methylamino)pyrimidine (IV), b₁₄ 91-2°, m. 59-61° (from petr. ether). 4-Hydroxypyrimidine (V) (7 g.) and 25 ml. POCl₃ refluxed 25 min., cooled, extracted with six 15-ml. portions of petr. ether to remove the POCl₃, and the residue treated with MeOH gave as with II, 4-methoxypyrimidine (VI), colorless liquid, b₃₀ 69-70°. 2,4-Dimercaptopyrimidine (VII) (10.2 g.) and 60 ml. 25% aqueous Me₂NH heated 3 hrs. at 130°, evaporated, the residue treated with 200 ml. cold 0.5N HCl (VII was insoluble), the mixture filtered, and the filtrate adjusted to pH 3-4 gave 8.25 g. 4-dimethylamino-2-mercaptopyrimidine (VIII), m. 265-78° (decomposition), which, treated in 370 ml. boiling H₂O portionwise with 45 g. (wet weight) Raney Ni, refluxed 0.5 hr., filtered hot, the insoluble material washed with 100 ml. hot H₂O, the combined filtrates treated with 20 g. Raney Ni as above, filtered, the filtrate saturated with salt, extracted 15 hrs. with Et₂O, and the extracts concentrated and distilled gave 3.1 g. 4-(dimethylamino)pyrimidine (IX), b₅₀ 131-2°, m. about 40° 2-Mercapto-4-(methylamino)pyrimidine (12 g.) and Raney Ni as above gave 54% 4-(methylamino)pyrimidine (X), b₁₆ 142-4°, m, 69-72° (from petr. ether). 2-Aminopyrimidine (XI) (0.48 g.) and 1.5 ml. Ac₂O refluxed 1 hr., cooled, and 5 ml. Me₂CO added gave 0.45 g. 2-acetamidopyrimidine, colorless laths, m. 145-6.5° [from AcCH₂CHMe (XII)]. 4-Amino-5-cyanopyrimidine (XIII), m. 248-51° (decomposition) (7.4 g.), 55 ml. N KOH, and 225 ml. 3% H₂O₂ kept 1 hr. at 50-5°, the pH adjusted to 7, and the solution cooled gave 5.6 g. 4-amino-5-pyrimidinecarboxamide, colorless laths, m. 254-6° (from H₂O). XIII (1.9 g.) and 19 ml. 2.5N NaOH heated 1 hr. on the steam bath, the pH adjusted to 4, and the whole cooled gave 1.75 g. 4-amino-5 pyrimidinecarboxylic acid (XV), m. 278-81° (from H₂O); XIV (4.25 g.) and 40 ml. 2.5N NaOH gave as above 3.8 g. XV. XV (0.5 g.) added in portions to 5 g. Ph₂CO at 280, kept 5 min. at 280°, cooled to 100°, 25 ml. petr. ether (b. 100-20°) added, and the mixture cooled gave 0.1 g. 4-aminopyrimidine (XVI), m. 150° (from XII); 4-acetamido analog, colorless needles, m. 198-200° (from XII.). The pK_a (for 0.01M solution unless otherwise stated) at 20°, pH (as buffered), λ_maximum and log ε_maximum for the following compounds are reported: V, 1.69 ± 0.04 (or 8.60 ± 0.02), 13 (or 6.2), 227, 263 (or 223, 260), 4.06, 3.56 (or 3.87, 3.57); VI, 2.5 ± 0.2, 6.95 (0), 247-8 (227-8, 238), 3.53 (3.89, 386); XI (0.1M), 3.54, 7.0 (1), 224, 292 (221, 302-3), 4.13, 350 (4.17, 360); IV 3.82, 0.03, 7.0 (1), 234, 306-7 (228, 315), 4.23, 4.33 (4.23, 3.53); III, 3.96 ± 0.01, 7.0 (1), 243, 318 (235, 324-5), 4.26, 3.35 (4.24, 3.47); XVI (0.005M), 5.71, 13 (0), 233, 268-9 (246), 4.26, 3.72 (4.27); X, 6.12 ± 0.04, 9.0 (2.1), 242, 276-7 (254), 4.18, 3.54 (4.20); and IX, 6.35 ± 0.02, 9.3 (3.15), 250, 286 (262), 4.22, 3.56 (4.21). The infrared absorption curves for 2-hydroxypyrimidine, II, V, and VI in CCl₄ are shown; XI and XVI show the 2 strong bands characteristic of the H₂N group, proving that these 2 compounds exist in that form in this solvent. The various spectra are discussed.

Journal of the Chemical Society 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, Related Products of pyrimidines.

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

Tereshchenkov, A. G. published the artcileInteraction of chloramphenicol tripeptide analogs with ribosomes, HPLC of Formula: 186046-81-1, the publication is Biochemistry (Moscow) (2016), 81(4), 392-400, database is CAplus and MEDLINE.

Chloramphenicol amine peptide derivatives containing tripeptide fragments of regulatory “stop peptides”-MRL, IRA, IWP-were synthesized. The ability of the compounds to form ribosomal complexes was studied by displacement of the fluorescent erythromycin analog from its complex with E. coli ribosomes. It was found that peptide chloramphenicol analogs are able to bind to bacterial ribosomes. The dissociation constants were 4.3-10 μM, which is 100-fold lower than the corresponding values for chloramphenicol amine-ribosome complex. Interaction of the chloramphenicol peptide analogs with ribosomes was simulated by mol. docking, and the most probable contacts of “stop peptide” motifs with the elements of nascent peptide exit tunnel were identified.

Biochemistry (Moscow) 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 C18H34N4O5S, HPLC of Formula: 186046-81-1.

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