Pyrimidines

Goldberg, Daniel R. published the artcileOptimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(3), 413-419, database is CAplus and MEDLINE.

As a follow-up to the discovery of our spirocyclic proline-based TPH1 inhibitor lead, we describe the optimization of this scaffold. Through a combination of X-ray co-crystal structure guided design and an in vivo screen, new substitutions in the lipophilic region of the inhibitors were identified. This effort led to new TPH1 inhibitors with in vivo efficacy when dosed as their corresponding Et ester prodrugs. In particular, 15b (KAR5585), the prodrug of the potent TPH1 inhibitor 15a (KAR5417), showed robust reduction of intestinal serotonin (5-HT) levels in mice. Furthermore, oral administration of 15b generated high and sustained systemic exposure of the active parent 15a in rats and dogs. KAR5585 was selected for further pharmacol. evaluation in disease models associated with a dysfunctional peripheral 5-HT system.

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 C4H3Cl2N3, Name: 2-Amino-4,6-dichloropyrimidine.

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

Markus, Tal Z. published the artcileThe Capture of Low-Energy Electrons by PNA versus DNA, 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 Journal of Physical Chemistry Letters (2013), 4(19), 3298-3302, database is CAplus.

This study provides insight into the mechanism of capturing low energy electrons by peptide nucleic acid (PNA) and the role of the oligonucleotide backbone in the capture of low energy electrons. We studied by photoemission self-assembled monolayers of two types of oligonucleotides, DNA and PNA. PNA is a synthetic analog of DNA that has a pseudopeptide backbone and which may have important medical and biotechnol. applications. We found that in both PNA and DNA, the guanine nucleobases capture the electrons more efficiently than thymines. In PNA, once the electrons are captured, their state is at least partially localized on the nucleobases, and the PNA mol. undergoes structural changes that stabilize the electron. This situation is in contrast to DNA, in which the captured electrons are transferred very efficiently to the backbone, and the final state of captured electron is base independent.

Journal of Physical Chemistry Letters 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

Fernandez-Cureses, Gloria published the artcileDesign, Synthesis, and Biological Evaluation of Unconventional Aminopyrimidine, Aminopurine, and Amino-1,3,5-triazine Methyloxynucleosides, Quality Control of 56-05-3, the publication is ChemMedChem (2015), 10(2), 321-335, database is CAplus and MEDLINE.

Herein we describe a class of unconventional nucleosides (methyloxynucleosides) that combine unconventional nucleobases such as substituted aminopyrimidines, aminopurines, or aminotriazines with unusual sugars in their structures. The allitollyl or altritollyl derivatives were pursued as ribonucleoside mimics, whereas the THF analogs were pursued as their dideoxynucleoside analogs. The compounds showed poor, if any, activity against a broad range of RNA and DNA viruses, including human immunodeficiency virus (HIV). This inactivity may be due to lack of an efficient metabolic conversion into their corresponding 5′-triphosphates and poor affinity for their target enzymes (DNA/RNA polymerases). Several compounds showed cytostatic activity against proliferating human CD4⁺ T-lymphocyte CEM cells and against several other tumor cell lines, including murine leukemia L1210 and human prostate PC3, kidney CAKI-1, and cervical carcinoma HeLa cells. A few compounds were inhibitory to Moloney murine sarcoma virus (MSV) in C₃H/3T3 cell cultures, with the 2,6-diaminotri-O-benzyl-D-allitolyl- and -D-altritolyl pyrimidine analogs being the most potent among them. This series of unconventional nucleosides may represent a novel family of potential antiproliferative agents.

ChemMedChem 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, Quality Control of 56-05-3.

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

Kumar, Brajesh published the artcileCoupling 6-chloro-3-methyluracil with copper: structural features, theoretical analysis, and biofunctional properties, Safety of 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Dalton Transactions (2021), 50(38), 13533-13542, database is CAplus and MEDLINE.

As nucleobases in RNA and DNA, uracil and 5-methyluracil represent a recognized class of bioactive mols. and versatile ligands for coordination compounds with various biofunctional properties. In this study, 6-chloro-3-methyluracil (Hcmu) was used as an unexplored building block for the self-assembly generation of a new bioactive copper(II) complex, [Cu(cmu)₂(H₂O)₂]·4H₂O (1). This compound was isolated as a stable crystalline solid and fully characterized in solution and solid state by a variety of spectroscopic methods (UV-vis, EPR, fluorescence spectroscopy), cyclic voltammetry, X-ray diffraction, and DFT calculations The structural, topol., H-bonding, and Hirshfeld surface features of 1 were also analyzed in detail. The compound 1 shows a distorted octahedral {CuN₂O₄} coordination environment with two trans cmu^– ligands adopting a bidentate N,O-coordination mode. The monocopper(II) mol. units participate in strong H-bonding interactions with water mols. of crystallization, leading to structural 0D → 3D extension into a 3D H-bonded network with a tfz-d topol. Mol. docking and ADME anal. as well as antibacterial and antioxidant activity studies were performed to assess the bioactivity of 1. In particular, this compound exhibits a prominent antibacterial effect against Gram neg. (E. coli, P. aeruginosa) and pos. (S. aureus, B. cereus) bacteria. The obtained copper(II) complex also represents the first structurally characterized coordination compound derived from 6-chloro-3-methyluracil, thus introducing this bioactive building block into a family of uracil metal complexes with notable biofunctional properties.

Dalton Transactions 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, Safety of 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Radhakrishnan, K. published the artcileSynthesis of Size-Expanded Nucleobase Analogues for Artificial Base-Pairing Using a Ligand-Free, Microwave-Assisted Copper(I)-Catalyzed Reaction, Safety of 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one, the publication is ChemistrySelect (2018), 3(46), 13098-13102, database is CAplus.

In order to incorporate valuable properties to the size-expanded nucleobases, a new catalog of highly substituted 2-aminoquinazolinone derivatives, e.g., I have been synthesized in a one-pot, microwave-directed reaction. Syntheses were carried out using simple reactants such as ortho-halo aromatic carboxylic acids, e.g., 4-bromo-3-thiophenecarboxylic acid and guanidine hydrochloride, in absence of any addnl. ligand. The usefulness of the methodol. could be justified by the diversity of the compounds synthesized, containing functional groups, natural nucleobases, fluorophores or peptide bonds.

ChemistrySelect published new progress about 897359-74-9. 897359-74-9 belongs to pyrimidines, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine,Amide, name is 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one, and the molecular formula is C7H5ClN4O, Safety of 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one.

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

Neidigh, Jonathan W. published the artcileCloning and Characterization of Rhodotorula glutinis Thymine Hydroxylase, Quality Control of 608-34-4, the publication is Chemical Research in Toxicology (2009), 22(5), 885-893, database is CAplus and MEDLINE.

Thymine hydroxylase (TH) is a member of the α-ketoglutarate-dependent nonheme iron dioxygenase family that includes a series of DNA repair proteins including alkB. Substantial interest in this family of enzymes derives from their capacity to modify DNA bases and precursors by oxidation Previously, a sequence has been published for cloned Rhodotorula glutinis TH. However, the minimal reported activity of this enzyme, coupled with inconsistencies with previously published mass spectrometry data, compelled us to reexamine TH. The sequence reported here differs from the previously reported sequence at two amino acid positions and is consistent with previously reported mass spectrometry data. The cloned enzyme characterized in this report displayed substantial activity, indicating that the sequence differences are critical for activity. The substrate selectivity of TH against a series of pyrimidine analogs is consistent with that reported for the wild-type enzyme and, in part, explains the mode of selection of uracil analogs. A preliminary model of the active site has been constructed for the purposes of comparing TH with other members of this family. TH and alkB share in common the capacity to oxidize N-Me groups. However, TH has the added capacity to oxidize the 5-Me group of thymine, a property that is potentially important for enzymes that could act on DNA and modify DNA-protein interactions.

Chemical Research in Toxicology 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, Quality Control of 608-34-4.

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

Debaene, Francois published the artcileExpanding the scope of PNA-encoded libraries: divergent synthesis of libraries targeting cysteine, serine and metallo-proteases as well as tyrosine phosphatases, Application In Synthesis of 172405-16-2, the publication is Tetrahedron (2007), 63(28), 6577-6586, database is CAplus.

Seven PNA-encoded combinatorial libraries targeting proteases and phosphatases with covalent reversible and irreversible mechanism-based inhibitors were prepared The libraries were synthesized using modified PNA monomers, which dramatically increase the water solubility of the libraries in biol. relevant buffers. The libraries were shown to selectively inhibit targeted enzymes.

Tetrahedron published new progress about 172405-16-2. 172405-16-2 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide, name is 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, and the molecular formula is C11H15N3O5, Application In Synthesis of 172405-16-2.

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

Ali, Juma A. M. published the artcilePyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines, Safety of 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Molecular Pharmacology (2013), 83(2), 439-453, database is CAplus and MEDLINE.

African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host. However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy. Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters. This transporter had low affinity for uridine and 2’deoxyuridine and was the sole pyrimidine transporter expressed in these cells. In addition, thymidine was taken up inefficiently through a P1-type nucleoside transporter. Of importance, the anticancer drug 5-fluorouracil was an excellent substrate for TbU3, and several 5-fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F-orotic acid, 5F-2’deoxyuridine displayed activity in the low micromolar range. The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains. The anal. showed that 5-fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA. 5F-2’dUrd and 5F-2’dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F-dUMP. We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome-wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes.

Molecular Pharmacology 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, Safety of 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Girault, Gisel published the artcileAmino derivatives of several nitrogen-containing heterocycles. II. Preparation, UV absorption, and ionization constants, HPLC of Formula: 31401-45-3, the publication is Bulletin de la Societe Chimique de France (1972), 2787-98, database is CAplus.

Uv spectral data are given ionization constants are determined for pyridines and pyrimidines containing an NH2, NHMe, or NMe2 group, 4-amino-, 4-methylamino-, and 4-dimethylaminoquinoline (I), and the corresponding 9-aminated acridines. Steric inhibition of conjugation is observed for I and 9-dimethylaminoacridine but not for 9-methylaminoacridine.

Bulletin de la Societe Chimique de France 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, HPLC of Formula: 31401-45-3.

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

Beaufils, Florent published the artcile5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, the publication is Journal of Medicinal Chemistry (2017), 60(17), 7524-7538, database is CAplus and MEDLINE.

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclin. characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1 as a clin. candidate with a broad application range in oncol., including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clin. trials for advanced solid tumors and refractory lymphoma.

Journal of Medicinal Chemistry published new progress about 944401-58-5. 944401-58-5 belongs to pyrimidines, auxiliary class Trifluoromethyl,Pyrimidine,Fluoride,Boronic acid and ester,Amine,Boronate Esters,Boronic acid and ester,, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, and the molecular formula is C11H15BF3N3O2, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine.

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