Category: pyrimidines

Lu, Xueyi published the artcileThe discovery of novel diarylpyri(mi)dine derivatives with high level activity against a wide variety of HIV-1 strains as well as against HIV-2, Related Products of pyrimidines, the publication is Bioorganic & Medicinal Chemistry (2018), 26(8), 2051-2060, database is CAplus and MEDLINE.

By structure-based mol. hybridization strategy, a series of novel diarylpyri(mi)dine derivatives targeting the entrance channel of HIV-1 reverse transcriptase (RT) were designed, synthesized and evaluated as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs). Encouragingly, all the tested compounds showed good activities against wild-type (WT) HIV-1 (IIIB) with EC₅₀ in the range of 1.36 nM-29 nM, which is much better than those of nevirapine (NVP, EC₅₀ = 125.42 nM) and azidothymidine (AZT, EC₅₀ = 11.36 nM). Remarkably, these compounds also displayed effective activity against the most of the single and double-mutated HIV-1 strains with low EC₅₀ values, which is comparable to the control drugs. Besides, these compounds were also exhibited favorable enzymic inhibitory activity. Moreover, preliminary structure-activity relationships (SARs) and mol. modeling study were investigated and discussed in detail. Unexpectedly, four diarylpyrimidines yielded moderate anti-HIV-2 activities. To the authors’ knowledge, this is rarely reported that diarylpyrimidine-based NNRTIs have potent activity against both HIV-1 and HIV-2 in cell culture.

Bioorganic & 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

Walunj, Manisha B. published the artcilePost-transcriptional labeling by using Suzuki-Miyaura cross-coupling generates functional RNA probes, Safety of 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is Nucleic Acids Research (2018), 46(11), e65/1-e65/10, database is CAplus and MEDLINE.

Pd-catalyzed C-C bond formation, an important vertebra in the spine of synthetic chem., is emerging as a valuable chemoselective transformation for post-synthetic functionalization of biomacromols. While methods are available for labeling protein and DNA, development of an analogous procedure to label RNA by cross-coupling reactions remains a major challenge. Herein, we describe a new Pd-mediated RNA oligonucleotide (ON) labeling method that involves post-transcriptional functionalization of iodouridine-labeled RNA transcripts by using Suzuki-Miyaura cross-coupling reaction. 5-Iodouridine triphosphate (IUTP) is efficiently incorporated into RNA ONs at one or more sites by T7 RNA polymerase. Further, using a catalytic system made of Pd(OAc)2 and 2-aminopyrimidine- 4,6-diol (ADHP) or dimethylamino-substituted ADHP (DMADHP), we established a modular method to functionalize iodouridine-labeled RNA ONs in the presence of various boronic acid and ester substrates under very mild conditions (37°C and pH 8.5). This method is highly chemoselective, and offers direct access to RNA ONs labeled with commonly used fluorescent and affinity tags and new fluorogenic environment-sensitive nucleoside probes in a ligand-controlled stereoselective fashion. Taken together, this simple approach of generating functional RNA ON probes by Suzuki-Miyaura coupling will be a very important addition to the resources and tools available for analyzing RNA motifs.

Nucleic Acids Research 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 C4H5NS2, Safety of 2-(Dimethylamino)pyrimidine-4,6-diol.

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

Shkurko, O. P. published the artcileEquilibrium NH-acidity of substituted aminopyrimidines, SDS of cas: 56621-93-3, the publication is Zhurnal Organicheskoi Khimii (1981), 17(2), 312-17, database is CAplus.

The transmetalation method was used to determine the NH acidity (pK) of thirty-nine 2-, 4-, and 5-aminopyrimidines; the pK values ranged from 17.7 for 5-nitro-2-pyrimidinamine to 30.2 for 2-(dimethylamino)-5-pyrimidinamine. Comparison with the pK of aniline showed that the ring N atoms had an acidifying effect in the order 4-aza ≫ 2-aza > 3-aza. LFER of the pK vs. NMR chem. shifts, and inductive or resonance substituent constants were described.

Zhurnal Organicheskoi Khimii published new progress about 56621-93-3. 56621-93-3 belongs to pyrimidines, auxiliary class Pyrimidine,Nitrile,Amine, name is 5-Aminopyrimidine-2-carbonitrile, and the molecular formula is C17H37NO3, SDS of cas: 56621-93-3.

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

Cohen, Sasson published the artcileThe preparation and properties of 6-halomethylpurines, Recommanded Product: N,N-Dimethylpyrimidin-4-amine, the publication is Journal of Organic Chemistry (1962), 3545-9, database is CAplus.

6-Methylpurine (I) was converted by sulfuryl chloride or N-chlorosuccinimide into 6-trichloromethylpurine in trifluoroacetic acid solution. Stepwise or partial chlorination of the methyl group was not achieved. N-Bromosuccinimide converted I into the 6-dibromo- and, by further substitution, 6-tribromomethylpurine. Stepwise catalytic reduction of the trihalomethylpurines afforded dihalo- and monohalomethylpurines. The chem. and phys. properties of the new compounds are described.

Journal of Organic Chemistry 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

Gower, Carrie M. published the artcileConversion of a Single Polypharmacological Agent into Selective Bivalent Inhibitors of Intracellular Kinase Activity, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is ACS Chemical Biology (2016), 11(1), 121-131, database is CAplus and MEDLINE.

Loss-of-function studies are valuable for elucidating kinase function and the validation of new drug targets. While genetic techniques, such as RNAi and genetic knockouts, are highly specific and easy to implement, in many cases post-translational perturbation of kinase activity, specifically pharmacol. inhibition, is preferable. However, due to the high degree of structural similarity between kinase active sites and the large size of the kinome, identification of pharmacol. agents that are sufficiently selective to probe the function of a specific kinase of interest is challenging, and there is currently no systematic method for accomplishing this goal. Here, the authors present a modular chem. genetic strategy that uses antibody mimetics as highly selective targeting components of bivalent kinase inhibitors. The authors demonstrate that it is possible to confer high kinase selectivity to a promiscuous ATP-competitive inhibitor by tethering it to an antibody mimetic fused to the self-labeling protein SNAPtag. With this approach, a potent bivalent inhibitor of the tyrosine kinase Abl was generated. Profiling in complex cell lysates, with competition-based quant. chem. proteomics, revealed that this bivalent inhibitor possesses greatly enhanced selectivity for its target, BCR-Abl, in K562 cells. Importantly, the authors show that both components of the bivalent inhibitor can be assembled in K562 cells to block the ability of BCR-Abl to phosphorylate a direct cellular substrate. Finally, the authors demonstrate the generality of using antibody mimetics as components of bivalent inhibitors by generating a reagent that is selective for the activated state of the serine/threonine kinase ERK2.

ACS Chemical Biology 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, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

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

Gambacorta, Augusto published the artcileHSAB-driven chemoselective N¹-alkylation of pyrimidine bases and their 4-methoxy- or 4-acetylamino-derivatives, HPLC of Formula: 608-34-4, the publication is Tetrahedron (2006), 62(29), 6848-6854, database is CAplus.

The lithium salts of the conjugated bases of 4-methoxy- and 4-acetylamino-2(1H)-pyrimidinone derivatives undergo highly chemoselective N¹-methylation or ethylation when treated with Me sulfate or Et sulfate (hard electrophiles) in dry dioxane, while the use of DMF as solvent results in competitive O²-alkylation. Potassium salts of the same bases in DMF undergo prevalent O²-attack. Under the same conditions, a similar but less chemoselective behavior is observed in alkylation of thymine and uracil, where some N³-attack occurs. This can be rationalized in terms of the HSAB principle.

Tetrahedron 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, HPLC of Formula: 608-34-4.

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

Hoang, Van-Hai published the artcileDiscovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design, Related Products of pyrimidines, the publication is Journal of Medicinal Chemistry (2017), 60(6), 2573-2590, database is CAplus and MEDLINE.

Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). The authors designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ_3E-42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 (I) significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an addnl. binding region into the authors’ previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu 327 in the QC binding site. The authors’ study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.

Journal of Medicinal Chemistry published new progress about 174456-28-1. 174456-28-1 belongs to pyrimidines, auxiliary class Pyrimidine,Alkynyl,Alcohol, name is 3-(Pyrimidin-5-yl)prop-2-yn-1-ol, and the molecular formula is C7H6N2O, Related Products of pyrimidines.

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

Dolman, Nigel P. published the artcileSynthesis and Pharmacology of Willardiine Derivatives Acting as Antagonists of Kainate Receptors, COA of Formula: C5H6N2O2, the publication is Journal of Medicinal Chemistry (2005), 48(24), 7867-7881, database is CAplus and MEDLINE.

The natural product willardiine, I (R = H), is an AMPA receptor agonist while 5-iodowillardiine, I (R = I), is a selective kainate receptor agonist. In an attempt to produce antagonists of kainate and AMPA receptors, analogs of willardiine with substituents at the N³ position of the uracil ring were synthesized. The N³-4-carboxybenzyl substituted analog II (Ar = C₆H₄CO₂H-4) was found to be equipotent at AMPA and GLU_K5-containing kainate receptors in the neonatal rat spinal cord. The N³-2-carboxybenzyl substituted analog II (Ar = C₆H₄CO₂H-2) proved to be a potent and selective GLU_K5 subunit containing kainate receptor antagonist when tested on native rat and human recombinant AMPA and kainate receptor subtypes. The GLU_K5 kainate receptor antagonist activity was found to reside in the S-enantiomer III (R = H) whereas its R enantiomer was almost inactive. 5-Iodo-substituted derivative III (R = I) was found to have enhanced potency and selectivity for GLU_K5.

Journal of Medicinal Chemistry 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, COA of Formula: C5H6N2O2.

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

Mamtimin, Xirali published the artcileAcidochromicity of a low-molecular-weight pyrimidine-based copolymer, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is Journal of Applied Polymer Science (2014), 131(23), 41174/1-41174/7, database is CAplus.

A new type of low-mol.-weight polypyrimidine in a π-conjugated main chain was prepared by a Grignard reaction between 2-amino-4,6-dichloropyrimidine and 1,4-dibromo-2,5-didodecyloxybenzene in the presence of [1,2-Bis(diphenylphosphino) ethane]dichloronickel(II). The structure of the copolymer was fully elucidated by Fourier transform IR spectroscopy, ¹H-NMR, and elemental anal. The copolymer had good solubility in common organic solvents. The copolymer displayed a bathochromic shift when protonated with an organic or inorganic acid in chloroform or THF. The copolymer depicted facile p-doping and good electron-transporting electrochem. properties in a 1M H₂SO₄ aqueous solution The copolymer showed a narrow polydispersity of 1.04. Thermogravimetric anal. showed that the copolymer had a certain thermal stability with no decomposition at 250° under N₂. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41174.

Journal of Applied Polymer Science 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, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

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

Inagaki, Masahito published the artcileN-Benzoyl-protected Peptide Nucleic Acid (PNA) Monomers Expand the Range of Nucleobases Available for PNA-DNA Chimera, Application In Synthesis of 169396-92-3, the publication is Chemistry Letters (2019), 48(4), 341-344, database is CAplus.

We synthesized N-benzoyl-protected peptide nucleic acid (PNA) monomers, which are robust under the conditions for deprotecting the 9-fluorenylmethoxycarbonyl (Fmoc) group by piperidine but are removable by aqueous ammonia and hence totally compatible with Fmoc-solid phase synthesis. This new invention expands the range of available nucleobase sequences, allowing us to use acid-sensitive PNA oligomers and purine nucleotides (both of which are difficult to use in the conventional methods) in the preparation of PNA-DNA chimeras to avoid the drawbacks of traditional PNAs.

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, Application In Synthesis of 169396-92-3.

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