Day: November 25, 2022

Suda, Atsushi published the artcileDesign and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors, Quality Control of 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(2), 1136-1141, database is CAplus and MEDLINE.

Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors, CH5164840 showed high binding affinity for N-terminal Hsp90α (K _d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC₅₀ = 0.15 μM, NCI-N87 IC₅₀ = 0.066 μM). CH5164840 displayed high oral bioavailability in mice (F = 70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition = 83%).

Bioorganic & Medicinal Chemistry Letters 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 C20H28BNO5, Quality Control of 56-05-3.

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

Novak, Igor published the artcileElectronic structure and biological activity of nucleobases, Formula: C5H6N2O2, the publication is Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (2005), 61A(11-12), 2771-2774, database is CAplus and MEDLINE.

HeI and HeII photoelectron spectra of 6-chloro-1,3-dimethyluracil have been measured. The assignment of the spectrum was made by comparison with photoelectron spectra of related compounds and by high-level OVGF calculations The electronic structure changes in substituted nucleobases are discussed on the basis of photoelectron spectroscopic data. The electronic structure data are compared with structure-activity relationships regarding enzyme inhibition and complex formation. The electronic structure data give some insight into the nature of binding between nucleobases’ derivatives and different enzymes whose activity they inhibit.

Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy 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, Formula: C5H6N2O2.

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

Shkurko, O. P. published the artcileVibrational spectra of monosubstituted pyrimidines, Quality Control of 31401-45-3, the publication is Zhurnal Prikladnoi Spektroskopii (1975), 23(5), 860-5, database is CAplus.

The ir and Raman spectra of 2-, 4-, and 5-monosubstituted pyrimidine derivatives were measured at 400-1600 cm-1 and the characteristic frequencies were assigned. The Raman spectra of the 2-substituted pyrimidines were characterized with strong polarized bands at 1075-95 (low intensity ir) belonging to the in-plane deformation vibration of the CH pyrimidine bonds, a 990-1000 (medium intensity ir) of the breathing vibrations of the ring at 720-870 of substituent-sensitive vibrations and with a medium depolarized band at 630-655 cm-1 (medium or strong in ir). The ir spectra show a strong band at 800-830 cm-1 (low in the Raman spectra) of the out-of plane CH vibrations. The 5-substituted derivatives show in the Raman spectra intensive polarized bands at 1080-1125 (in plane CH deformation) and at 720-860 cm-1 (substituent-sensitive vibrations) and a medium band at 610-40 cm-1. The ir spectra show, in analogy with 1,3,5-trisubstituted benzene, strong bands at 860-900 and 710-730 cm-1. The Raman spectra of the 4-monosubstituted pyrimidines are characterized with strong polarized bands at 980-95 (“breathing” vibrations) and at 720-870 cm-1 both frequencies are of medium intensity in the ir. The bands at 1100 and 610-640 cm-1 observed at 2- and 5-substituted pyrimidines are absent. The ir spectra show intense bands of the out-of-plane CH deformation vibrations at 800-850 cm-1 which are of low intensity in the Raman spectrum.

Zhurnal Prikladnoi Spektroskopii 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 C14H17FN4O3, Quality Control of 31401-45-3.

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

Meguellati, Kamel published the artcileDNA-Templated Synthesis of Trimethine Cyanine Dyes: A Versatile Fluorogenic Reaction for Sensing G-Quadruplex Formation, Quality Control of 186046-81-1, the publication is Angewandte Chemie, International Edition (2010), 49(15), 2738-2742, S2738/1-S2738/17, database is CAplus and MEDLINE.

The fluorogenic synthesis of a sym. or unsym. trimethine cyanine dye by an aldolization-elimination reaction between two nonfluorescent precursors was applied for sensing G-quadruplex formation in vitro. Two peptide nucleic acids PNAs were designed that can each hybridize in a sequence-specific manner with five nucleobases upstream and five nucleobases downstream of the parallel-stranded ckit21T quadruplex chosen as a model system. They were functionalized at their C-terminal or N-terminal end with either an N-alkyl-2-methyleneindoline (Ind1-3) or an N-alkyl-2-(3,3-dimethylindolin-2-ylidene)acetaldehyde (Aid). Two ε-N,N-dimethyllysine residues per PNA strand were also added to ensure solubility of both PNAs in water at near-physiol. pH.

Angewandte Chemie, International Edition 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, Quality Control of 186046-81-1.

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

Gad, Helge published the artcileMTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Nature (London, United Kingdom) (2014), 508(7495), 215-221, database is CAplus and MEDLINE.

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, the authors show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. The authors validate MTH1 as an anticancer target in vivo and describe small mols. TH287 (I) and TH588 (II) as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

Nature (London, United Kingdom) 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, Name: 2-Amino-4,6-dichloropyrimidine.

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

Samijlenko, S. P. published the artcileSpecific interactions of deprotonated carboxylic group with uracil and thymine provoke diketo → keto-enol tautomeric transition in bases., Related Products of pyrimidines, the publication is Ukrains’kii Biokhimichnii Zhurnal (2001), 73(4), 128-131, database is CAplus.

The H¹ NMR and MNDO/H calculation data combined indicate the uracil and thymine tautomeric transitions from the ground diketo tautomeric state to the high-energy keto-enol one stimulated by specific interaction with carboxylate ion in anhydrous DMSO, which is blocked by base methylation at the 1 or 3 positions.

Ukrains’kii Biokhimichnii Zhurnal 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, Related Products of pyrimidines.

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

Stepanyugin, A. V. published the artcileUV spectra of pyrimidine bases and nucleosides in the context of methyl substitution and interaction with amino acid carboxylic group, Computed Properties of 608-34-4, the publication is Biopolimeri i Klitina (2003), 19(1), 43-63, database is CAplus.

UV spectra of pyrimidine nucleotide bases, nucleosides, a number of their derivatives and analogs were investigated in anhydrous DMSO. Effects of interaction with neutral and deprotonated carboxylic group of amino acids on the UV spectra were traced. It was established that methylation of pyrimidine bases at the positions 1 and S leads to the 5-12 nm bathochromic shift of the absorption bands. The majority of the Cyt derivatives excluding m³ Cyt and isoCyt were shown to interact specifically with neutral carboxylic group. Interactions with deprotonated carboxylic group is characteristic of Ura, Thy and their derivatives, except chx¹Ura, s²Ura and dU. The conclusion was drawn that substitution at the positions 1 and 5 is accompanied by a decrease of a complex formation ability with the both forms of carboxylic groups, but substitution at the position 5 strengthens interaction with neutral carboxylic group but decreases interaction with carboxylate-ion. Biol. significance of the results obtained is 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 C4H12ClNO, Computed Properties of 608-34-4.

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

Zhang, Zhaoda published the artcileHeteroditopic Binding of Magnetic Resonance Contrast Agents for Increased Relaxivity, Application In Synthesis of 186046-81-1, the publication is Angewandte Chemie, International Edition (2011), 50(11), 2621-2624, S2621/1-S2621/12, database is CAplus and MEDLINE.

We have shown that the small structural perturbation of incorporating a PNA (peptide nucleic acid) group into a fibrin-targeted contrast agent has a profound impact on relaxivity. The PNA moiety increases mol. weight by 3% but increases relaxivity by 50% compared to Gd2-Gly2-Pep-Gd2. The effect of the PNA group on relaxivity is the equivalent of synthesizing an agent with six GdDTPA moieties to achieve equivalent relaxivity. The PNA group has a modest pos. impact on fibrin binding and serves to rigidify the N-terminal portion of the mol. upon fibrin binding. Importantly, the PNA group does not increase non-specific protein binding. As a result, relaxivity of Gd2-T-Pep-Gd2 bound to fibrin is more than 50% increased compared to Gd2-Pep-Gd2 while the relaxivity of the two compounds in plasma is comparable. This should result in much greater clot blood contrast for Gd2-T-Pep-Gd2.

Angewandte Chemie, International Edition 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 C8H8O2, Application In Synthesis of 186046-81-1.

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

Zhang, Zhaoda published the artcileHeteroditopic Binding of Magnetic Resonance Contrast Agents for Increased Relaxivity, Recommanded Product: 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, the publication is Angewandte Chemie, International Edition (2011), 50(11), 2621-2624, S2621/1-S2621/12, database is CAplus and MEDLINE.

We have shown that the small structural perturbation of incorporating a PNA (peptide nucleic acid) group into a fibrin-targeted contrast agent has a profound impact on relaxivity. The PNA moiety increases mol. weight by 3% but increases relaxivity by 50% compared to Gd2-Gly2-Pep-Gd2. The effect of the PNA group on relaxivity is the equivalent of synthesizing an agent with six GdDTPA moieties to achieve equivalent relaxivity. The PNA group has a modest pos. impact on fibrin binding and serves to rigidify the N-terminal portion of the mol. upon fibrin binding. Importantly, the PNA group does not increase non-specific protein binding. As a result, relaxivity of Gd2-T-Pep-Gd2 bound to fibrin is more than 50% increased compared to Gd2-Pep-Gd2 while the relaxivity of the two compounds in plasma is comparable. This should result in much greater clot blood contrast for Gd2-T-Pep-Gd2.

Angewandte Chemie, International Edition 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 C7H11N3O2, Recommanded Product: 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.

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

Socher, Elke published the artcileDual fluorophore PNA FIT-probes – extremely responsive and bright hybridization probes for the sensitive detection of DNA and RNA, COA of Formula: C39H35N5O8, the publication is Organic & Biomolecular Chemistry (2012), 10(36), 7363-7371, database is CAplus and MEDLINE.

Fluorescently labeled oligonucleotides are commonly employed as probes to detect specific DNA or RNA sequences in homogeneous solution Useful probes should experience strong increases in fluorescent emission upon hybridization with the target. Dual labeled peptide nucleic acid probes were developed which signal the presence of complementary DNA or RNA by up to 450-fold enhancements of fluorescence intensity. This enabled the very sensitive detection of a DNA target (40 pM LOD), which was detectable at less than 0.1% of the beacon concentration In contrast to existing DNA-based mol. beacons, this PNA-based method does not require a stem sequence to enforce dye-dye communication. Rather, the method relies on the energy transfer between a “smart” thiazole orange (TO) nucleotide, which requires formation of the probe-target complex in order to become fluorescent, and terminally appended acceptor dyes. To improve upon fluorescence responsiveness the energy pathways were dissected. Hydrophobic, spectrally mismatched dye combinations allowed significant (99.97%) decreases of background emission in the absence of a target. By contrast, spectral overlap between TO donor emission and acceptor excitation enabled extremely bright FRET signals. This and the large apparent Stokes shift (82 nm) suggests potential applications in the detection of specific RNA targets in biogenic matrixes without the need of sample pre-processing prior to detection.

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 C12H14IN, COA of Formula: C39H35N5O8.

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