Tag: M.W=150-200

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

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

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

Ruiz Ruiz, Maria del Carmen published the artcileThe ‘t-Amino Effect’ of ortho-nitroso amines. synthesis of 2,6-diaminoadenine derivatives from 6-(dialkylamino)-5-nitrosopyrimidines, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Helvetica Chimica Acta (2011), 94(5), 785-800, database is CAplus.

The ‘t-amino effect’ of amino-nitroso compounds was documented by preparing the (dialkylamino)-nitroso pyrimidines, and cyclising them under thermal conditions in high yields to the purine derivatives e. g., I(R¹ = Me, R² = H, Me, Pr, Ph; R¹ = Et, R² = Me; R¹ = CO₂Et, R² = CH₂CO₂Et) and II. The reactivity of the amino-nitroso-pyrimidines, particularly of 17 derived from di-Et iminodiacetate, and of I(R¹ = CO₂Et, R² = CH₂CO₂Et), derived from 1-phenylimidazolidine, correlates with the stability of the intermediate azomethine ylide. Thermolysis of the amino-nitroso-pyrimidines III(R¹ = NO, R² = 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 4-Et isonipecotate-1yl) possessing dialkylamino substituents at C(4) and C(6), proceeded by protiodenitrosation, leading to III(R¹ = H, R² = 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 4-Et isonipecotate-1yl).

Helvetica Chimica Acta 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, Safety of 2-Amino-4,6-dichloropyrimidine.

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

Giordanetto, Fabrizio published the artcileDiscovery of phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance, SDS of cas: 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(21), 6671-6676, database is CAplus and MEDLINE.

Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor with favorable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Addnl., due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats.

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, SDS of cas: 56-05-3.

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

Santandrea, Ernesto published the artcileDevelopment of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge, Product Details of C4H3Cl2N3, the publication is Organic Process Research & Development (2021), 25(5), 1190-1205, database is CAplus.

The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities. The extensive optimization of the N-methylation of a Boc-protected amine with di-Me sulfate and of a nucleophilic aromatic substitution without the use of metal catalysts led to a robust, scalable process. The process was demonstrated on a >100 kg scale. Overall, improved drug substance quality, higher yield, and reduction of the process mass intensity were achieved.

Organic Process Research & Development 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, Product Details of C4H3Cl2N3.

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

Henderson, Scott H. published the artcileDiscovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors, Related Products of pyrimidines, the publication is Journal of Medicinal Chemistry (2021), 64(15), 11709-11728, database is CAplus and MEDLINE.

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) regulates the proliferation and differentiation of neuronal progenitor cells during brain development. Consequently, DYRK1A has attracted interest as a target for the treatment of neurodegenerative diseases, including Alzheimer′s disease (AD) and Down′s syndrome. Recently, the inhibition of DYRK1A has been investigated as a potential treatment for diabetes, while DYRK1A′s role as a mediator in the cell cycle has garnered interest in oncol. indications. Structure-activity relationship (SAR) anal. in combination with high-resolution X-ray crystallog. leads to a series of pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochem. properties, and a high degree of selectivity over the kinome. Compound 11 (I) exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the treatment of diseases linked to DYRK1A function.

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, Related Products of pyrimidines.

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

Dumas, Anaelle published the artcileSelf-Liganded Suzuki-Miyaura Coupling for Site-Selective Protein PEGylation, Application of 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is Angewandte Chemie, International Edition (2013), 52(14), 3916-3921, database is CAplus and MEDLINE.

PEG-boronic acids, in the presence of simple Pd sources, are capable of acting as direct and effective Suzuki reagents in 70-98% yield. When combined with non-natural amino acids, they allow efficient and direct, site-selective PEGylation of proteins at predetermined positions under biol. compatible conditions without the need for exogenous ligands.

Angewandte Chemie, International Edition 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, Application of 2-(Dimethylamino)pyrimidine-4,6-diol.

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

Camacho-Hernandez, Gisela Andrea published the artcileSynthesis, pharmacological characterization, and structure-activity relationships of non-canonical selective agonists for α7 nAChRs, Application of 2-Amino-4,6-dichloropyrimidine, the publication is Journal of Medicinal Chemistry (2019), 62(22), 10376-10390, database is CAplus and MEDLINE.

Noncanonical 2,4,6-substituted pyrimidine analogs were prepared for a structure-activity relationship study. The new lead compounds activate selectively the α7 nAChRs with EC₅₀‘s between 30-140 nM in a PNU-120596-dependent, cell-based calcium influx assay. After characterizing the expanded lead landscape, author ranked the compounds for rapid activation using Xenopus oocytes expressing human α7 nAChR with a two-electrode voltage clamp. This approach enabled us to define the mol. determinants governing rapid activation, agonist potency, and desensitization of α7 nAChRs after exposure to pyrimidine analogs, thereby distinguishing this subclass of non-canonical agonists from previously defined types of agonists (agonists, partial agonists, silent agonists, and ago-PAMs). By NMR, author analyzed pKa values for ionization of lead candidates, demonstrating distinctive modes of interaction for this landscape of ligands.

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, Application of 2-Amino-4,6-dichloropyrimidine.

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