Day: November 21, 2022

Norcross, Neil R. published the artcileTrisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials, Synthetic Route of 56-05-3, the publication is Journal of Medicinal Chemistry (2016), 59(13), 6101-6120, database is CAplus and MEDLINE.

In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound I showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED₉₀ of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P 450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead mol. with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting.

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, Synthetic Route of 56-05-3.

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

Gustavsson, Thomas published the artcileSinglet Excited-State Behavior of Uracil and Thymine in Aqueous Solution: A Combined Experimental and Computational Study of 11 Uracil Derivatives, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Journal of the American Chemical Society (2006), 128(2), 607-619, database is CAplus and MEDLINE.

The excited-state properties of uracil, thymine, and nine other derivatives of uracil have been studied by steady-state and time-resolved spectroscopy. The excited-state lifetimes were measured using femtosecond fluorescence upconversion in the UV. The absorption and emission spectra of five representative compounds have been computed at the TD-DFT level, using the PBE0 exchange-correlation functional for ground- and excited-state geometry optimization and the polarizable continuum model (PCM) to simulate the aqueous solution The calculated spectra are in good agreement with the exptl. ones. Experiments show that the excited-state lifetimes of all the compounds examined are dominated by an ultrafast (< 100 fs) component. Only 5-substituted compounds show more complex behavior than uracil, exhibiting longer excited-state lifetimes and biexponential fluorescence decays. The S₀/S₁ conical intersection, located at CASSCF (8/8) level, is indeed characterized by pyramidalization and out of plane motion of the substituents on the C5 atom. A thorough anal. of the excited-state potential energy surfaces, performed at the PCM/TD-DFT(PBE0) level in aqueous solution, shows that the energy barrier separating the local S₁ min. from the conical intersection increases going from uracil through thymine to 5-fluorouracil, in agreement with the ordering of the exptl. excited-state lifetime.

Journal of the American Chemical Society 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

Asanuma, Hiroyuki published the artcilePrecise recognition of nucleotides and their derivatives through hydrogen bonding in water by poly(vinyldiaminotriazine), Product Details of C5H6N2O2, the publication is Supramolecular Science (1998), 5(3-4), 405-410, database is CAplus.

In water, poly(2-vinyl-4,6-diamino-1,3,5-triazine) (PVDAT) selectively binds the derivatives of thymine and uracil through the formation of three hydrogen bonds with the diaminotriazine (DAT) residues. The nucleotides and dinucleotides are bound much more strongly than are nucleic acid bases, due to the addnl. interactions of their phosphates with the DAT residues. The binding constant of the thymidine 5′-monophosphate-PVDAT adduct (5400 M^-1) is one of the largest values ever reported for the artificial receptors in protic solvents. In contrast, cytosine and its monophosphate are hardly bound to PVDAT. A water-soluble vinyldiaminotriazine-acrylamide copolymer also forms hydrogen bonds with thymine in water, whereas the corresponding monomers do not. A polymer effect is predominantly important for the mol. recognition through hydrogen bonding in water.

Supramolecular Science 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, Product Details of C5H6N2O2.

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

Murata, Tsuyoshi published the artcileSingle-component organic conductors based on neutral betainic radicals of N-methyl substituted dioxo- and aminooxo-pyrimido-fused TTFs, Related Products of pyrimidines, the publication is Synthetic Metals (2008), 158(12), 497-505, database is CAplus.

New dioxo- and aminooxo-pyrimido-fused tetrathiafulvalene (TTF) derivatives, whose pyrimido-rings are substituted by Me group, were synthesized. In the crystal structures of their tetrabutylammonium salts, complementary hydrogen-bonds inherent in pyrimido-fused TTF derivatives were inhibited by the Me substitution, and the crystals were constructed by the segregated motifs of cations and anions. Betainic radicals prepared by one-electron oxidation of tetrabutylammonium salts exhibited relatively high conductivities (ca. 10^-4 S cm^-1 at room temperature) as single-component organic mols. The optical measurement of betainic radicals showed considerably low-energy charge-transfer absorption between radical mols. compared to those of conventional TTF systems, indicating the reduction of on-site Coulomb repulsion.

Synthetic Metals 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, Related Products of pyrimidines.

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

Portalone, Gustavo published the artcileThe crystal structure of 3-methyluracil from X-ray powder diffraction data, Category: pyrimidines, the publication is Journal of Molecular Structure (2002), 608(1), 35-39, database is CAplus.

The crystal structure of 3-methyluracil was determined ab initio from conventional monochromatic x-ray powder diffraction data. The crystals are orthorhombic, space group Pbnm, with a 6.6294(1), b 13.1816(3), c 6.53938(9) (Å); Z = 8. The structure was solved by direct methods and the final Rietveld refinement converged to R_p = 0.0398, R_wp = 0.0528, R_Bragg = 0.0294. The crystal structure exhibits endless chains of planar mols., connected via head-to-tail N-H…O H bonds.

Journal of Molecular Structure 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

Neunhoeffer, Hans published the artcileCycloaddition reactions with azabenzenes. X. Cycloaddition reactions with 1,3,5-triazines, Recommanded Product: N,N-Dimethylpyrimidin-4-amine, the publication is Chemische Berichte (1975), 108(12), 3877-82, database is CAplus.

Triazines I (R1, R2, R3 = H, Me, CO2Et, Cl) reacted with electron-rich dienophiles [MeCCNEt2, II, EtOC(NMe2):CHR3 (R3 = H, Me)] and with electron-poor dienophiles (MeO2CCCCO2Me) by a (4+2)-cycloaddition reaction to give pyrimidines III [R4 = R1, R5 = R3, R6 = Me, R7 = NEt2; R4 = R5 = H, R6 = H, CO2Me, R7 = OEt, NMe2, CO2Me; R6R7 = (CH2)3]. I (R3 = Me) reacted with EtOC(NMe2):CHR8 (R8 = H, Me) to give vinyltriazines I [R3 = CH:C(NMe2)CH2R8]. I [R3 = CH:C(NMe2)CH2] reacted with di-Me 1,2,4,5-tetrazine-3,6-dicarboxylate to give pyridazinyltriazines IV.

Chemische Berichte 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

Bantzi, Marina published the artcileNovel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer, Computed Properties of 459420-09-8, the publication is Journal of Medicinal Chemistry (2021), 64(9), 6221-6240, database is CAplus and MEDLINE.

The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H₂S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. Authours now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H₂S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST’s active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (2-((2-(Naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one) was also confirmed on the growth of MC38 tumors in mice.

Journal of Medicinal Chemistry published new progress about 459420-09-8. 459420-09-8 belongs to pyrimidines, auxiliary class Metabolic Enzyme,3MST, name is 6-Methyl-2-((2-(naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one, and the molecular formula is C17H14N2O2S, Computed Properties of 459420-09-8.

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

Noda, Hidetoshi published the artcileA C4N4 Diaminopyrimidine Fluorophore, COA of Formula: C4H3Cl2N3, the publication is Chemistry – A European Journal (2019), 25(17), 4299-4304, database is CAplus and MEDLINE.

A new scaffold for producing efficient organic fluorescent materials was identified: 2,5-diamino-4,6-diarylpyrimidine featuring a C4N4 elemental composition Single-step installation of two aryl groups at the 4,6-positions of the pyrimidine core delivered fluorescent organic materials in a modular fashion. A range of fluorescent compounds with distinct absorption/emission properties was readily accessed by changing the aromatic attachments. A generally high absorption coefficient and quantum yield were observed, including C4N4 derivatives that could fluoresce even in the solid state. The two amino groups at the 2,5-positions of the pyrimidine were essential for intense fluorescence with a large Stokes shift, which was corroborated by structural relaxation to a p-iminoquinone-like structure in the excited state. Besides live-cell imaging capabilities, fluorescent labeling of a protein involved in autophagy elucidated a new protein-protein interaction, supporting potential utility in bioimaging applications.

Chemistry – A European Journal 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, COA of Formula: C4H3Cl2N3.

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

Deuss, Peter J. published the artcileParallel synthesis and splicing redirection activity of cell-penetrating peptide conjugate libraries of a PNA cargo, Computed Properties of 186046-81-1, the publication is Organic & Biomolecular Chemistry (2013), 11(43), 7621-7630, database is CAplus and MEDLINE.

A novel method for the parallel synthesis of peptide-biocargo conjugates was developed that utilizes affinity purification for fast isolation of the conjugates in order to avoid time consuming HPLC purification The methodol. was applied to create two libraries of cell-penetrating peptide (CPP)-PNA705 conjugates from parallel-synthesized peptide libraries. The conjugates were tested for their ability to induce splicing redirection in HeLa pLuc705 cells. The results demonstrate how the novel methodol. can be applied for screening purposes in order to find suitable CPP-biocargo combinations and further optimization of CPPs.

Organic & Biomolecular 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, Computed Properties of 186046-81-1.

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

Deuss, Peter J. published the artcileParallel synthesis and splicing redirection activity of cell-penetrating peptide conjugate libraries of a PNA cargo, HPLC of Formula: 169396-92-3, the publication is Organic & Biomolecular Chemistry (2013), 11(43), 7621-7630, database is CAplus and MEDLINE.

A novel method for the parallel synthesis of peptide-biocargo conjugates was developed that utilizes affinity purification for fast isolation of the conjugates in order to avoid time consuming HPLC purification The methodol. was applied to create two libraries of cell-penetrating peptide (CPP)-PNA705 conjugates from parallel-synthesized peptide libraries. The conjugates were tested for their ability to induce splicing redirection in HeLa pLuc705 cells. The results demonstrate how the novel methodol. can be applied for screening purposes in order to find suitable CPP-biocargo combinations and further optimization of CPPs.

Organic & Biomolecular 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, HPLC of Formula: 169396-92-3.

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