Category: pyrimidines

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

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

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

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

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

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

Zielenkiewicz, Wojciech published the artcileHeat Capacities of Uracil, Thymine, and Its Alkylated, Cyclooligomethylenated, and Halogenated Derivatives by Differential Calorimetry, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Journal of Chemical & Engineering Data (2007), 52(1), 93-97, database is CAplus.

The molar heat capacity (C_p) of solid uracil, its alkylated and halogenated derivatives, and cyclooligomethylenouracils in the temperature range of (298.15 to 343.15) K by a differential scanning calorimeter (SETARAM TG-DSC 111) were determined It was demonstrated that the C_p value increases by increasing the number of methylene groups attached to the diketo-pyrimidine ring. The correlations C_p = f(T) are given. The contributions of C-CH₃, N-CH₃, and C-NO₂ groups as well as F, Cl, Br, and I atoms in the value of C_p for the temperature of 298.15 K are presented. The Chickos method for calculation of C_p values is discussed.

Journal of Chemical & Engineering Data 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 C10H10O3, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Farand, Julie published the artcileDiscovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation, Related Products of pyrimidines, the publication is ACS Medicinal Chemistry Letters (2020), 11(3), 358-364, database is CAplus and MEDLINE.

We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncol. target, culminating in target (in)validation. Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC₅₀ = 0.043 nM). Cocrystn. of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramol. hydrogen bond and polar interactions with residues Gly34 and Asp120. Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC₅₀ = 0.49 nM). Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat. Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small mol. inhibition was studied. Based on our findings, we were unable to provide evidence to further pursue MTH1 as an oncol. target.

ACS 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 C4H3Cl2N3, Related Products of pyrimidines.

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

Brodyagin, Nikita published the artcilePyridazine Nucleobase in Triplex-Forming PNA Improves Recognition of Cytosine Interruptions of Polypurine Tracts in RNA, 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 ACS Chemical Biology (2021), 16(5), 872-881, database is CAplus and MEDLINE.

Sequence specific recognition of regulatory noncoding RNAs would open new possibilities for fundamental science and medicine. However, mol. recognition of such complex double-stranded RNA (dsRNA) structures remains a formidable problem. Recently, we discovered that peptide nucleic acids (PNAs) form an unusually stable and sequence-specific triple helix with dsRNA. Triplex-forming PNAs could become universal tools for recognition of noncoding dsRNAs but are limited by the requirement of polypurine tracts in target RNAs as only purines form stable Hoogsteen hydrogen bonded base triplets. Herein, we systematically surveyed simple nitrogen heterocycles P_N as modified nucleobases for recognition of cytosine in P_N*C-G triplets. We found that a 3-pyridazinyl nucleobase formed significantly more stable P_N*C-G triplets than other heterocycles including the pyrimidin-2-one previously used by us and others for recognition of cytosine interruptions in polypurine tracts of PNA-dsRNA triplexes. Our results improve triple helical recognition of dsRNA and provide insights for future development of new nucleobases to expand the sequence scope of noncoding dsRNAs that can be targeted by triplex-forming PNAs.

ACS Chemical Biology 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, 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

Hirano, Taisuke published the artcilePeptide-nucleic acids (PNAs) with pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone (PPT) as a universal base: their synthesis and binding affinity for oligodeoxyribonucleotides, Safety of 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 Organic & Biomolecular Chemistry (2009), 7(14), 2905-2911, database is CAplus and MEDLINE.

Peptide-nucleic acids (PNAs) including pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone (PPT) as a nucleobase were synthesized, and their binding affinity for the complementary oligodeoxyribonucleotides was investigated. The authors found that PNAs with one or two PPT(s) and natural nucleobases (i.e., adenine, cytosine, guanine, or thymine) have excellent binding affinity for oligodeoxyribonucleotides with complementary bases at the positions facing the natural nucleobases, and with adenine, cytosine, guanine, and thymine at the positions opposite PPT in PNAs. The binding affinity of the PPT-containing PNA is higher than or comparable to that of a PNA consisting of all complementary natural nucleobases, viz. a PNA with a suitable natural nucleobase in place of PPT in the PPT-containing PNA. Consequently, it was concluded that PPT serves as a useful universal base that can recognize all natural nucleobases.

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, Safety of 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