Pyrimidines

Camacho-Hernandez, Gisela Andrea published the artcileSynthesis, pharmacological characterization, and structure-activity relationships of non-canonical selective agonists for α7 nAChRs, Application of 2-Amino-4,6-dichloropyrimidine, the publication is Journal of Medicinal Chemistry (2019), 62(22), 10376-10390, database is CAplus and MEDLINE.

Noncanonical 2,4,6-substituted pyrimidine analogs were prepared for a structure-activity relationship study. The new lead compounds activate selectively the α7 nAChRs with EC₅₀‘s between 30-140 nM in a PNU-120596-dependent, cell-based calcium influx assay. After characterizing the expanded lead landscape, author ranked the compounds for rapid activation using Xenopus oocytes expressing human α7 nAChR with a two-electrode voltage clamp. This approach enabled us to define the mol. determinants governing rapid activation, agonist potency, and desensitization of α7 nAChRs after exposure to pyrimidine analogs, thereby distinguishing this subclass of non-canonical agonists from previously defined types of agonists (agonists, partial agonists, silent agonists, and ago-PAMs). By NMR, author analyzed pKa values for ionization of lead candidates, demonstrating distinctive modes of interaction for this landscape of ligands.

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, Application of 2-Amino-4,6-dichloropyrimidine.

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

Potyahaylo, A. L. published the artcileProton acceptor and proton donor properties of modified nucleotide bases and their complexing ability: quantum chemical investigation, Category: pyrimidines, the publication is Biopolimeri i Klitina (2004), 20(1-2), 62-70, database is CAplus.

Proton acceptor and proton donor properties of 40 modified nucleotide bases have been investigated by the AM1 semiempirical quantum chem. method, proven to be rather good for such tasks and matters. Based on the data obtained, the orders of the acidity and basicity have been built. The authors have also concluded about the character of self- and hetero-association of some modified nucleotide bases and their specific interactions with both neutral and deprotonated carboxylic groups of amino acids in vacuum. Biol. significance of these findings is briefly discussed.

Biopolimeri i Klitina 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, Category: pyrimidines.

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

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