Month: October 2022

Li, Si; Wu, Bin; Zheng, Xu; Wang, Changyuan; Zhao, Jingyuan; Sun, Huijun; Sun, Xiuli; Tang, Zeyao; Yuan, Hong; Chen, Lixue; Ma, Xiaodong published an article on January 31 ,2021. The article was titled 《Synthesis and biological activity of imidazole group-substituted arylaminopyrimidines (IAAPs) as potent BTK inhibitors against B-cell lymphoma and AML》, and you may find the article in Bioorganic Chemistry.Synthetic Route of C12H6ClN3O3S The information in the text is summarized as follows:

Bruton’s tyrosine kinase (BTK) is a member of the Tec kinase family and plays a key role in the modulation of the B-cell receptor (BCR)-mediated signaling pathway. Inhibition of BTK has been proven to be an effective therapeutic approach for various hematol. malignancies, such as chronic lymphocytic leukemia (CLL), mantle cell leukemia (MCL), diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML). Here, a new series of imidazole group-substituted arylaminopyrimidines (IAAPs) were designed and synthesized as potent inhibitors of the enzymic activity of BTK with a half maximal inhibitory concentration (IC50) ranging from 13.10 to 42.40 nM. In particular, 11a and 11b exhibited stronger antiproliferative activity against AML and B lymphomas cell lines compared with BTK inhibitor ibrutinib and showed low cytotoxicity against normal peripheral blood mononuclear cells (PBMCs). In addition, anal. of the mechanism of action of these compounds revealed that 11a and 11b induced significant apoptosis in AML and B lymphoma cells by arresting the cell cycle at the G1/G0 or G2/M stage and blocked BTK autophosphorylation as well as the ensuing abrogation of pro-survival AKT and ERK signaling. Taken together, these results suggest that 11a and 11b might serve as valuable preclin. candidates for the treatment of AML and B-cell lymphoma. After reading the article, we found that the author used 2-Chloro-4-(3-nitrophenoxy)thieno[3,2-d]pyrimidine(cas: 1353553-07-7Synthetic Route of C12H6ClN3O3S)

2-Chloro-4-(3-nitrophenoxy)thieno[3,2-d]pyrimidine(cas: 1353553-07-7) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Synthetic Route of C12H6ClN3O3S

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2014,Liu, Qiang; Fan, Wei; Tian, Hongqi published 《A highly efficient TfOH-assisted alkylation of azaindoles with α-phenylethanols》.Tetrahedron Letters published the findings.Reference of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The information in the text is summarized as follows:

A highly efficient TfOH-assisted alkylation of azaindoles with α-phenylethanols was developed. Under the optimal reaction condition, 3-(α-methylbenzyl)azaindoles were obtained in 98% yield. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Reference of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Reference of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineThey have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2016,Wang, Mengzhou; Zhang, Yanyan; Wang, Tao; Wang, Chao; Xue, Dong; Xiao, Jianliang published 《Story of an Age-Old Reagent: An Electrophilic Chlorination of Arenes and Heterocycles by 1-Chloro-1,2-benziodoxol-3-one》.Organic Letters published the findings.Formula: C6H3Cl2N3 The information in the text is summarized as follows:

By the use of 1-chloro-1,2-benziodoxol-3-one, an age-old reagent, the practical and efficient chlorination method is achieved. This hypervalent iodine reagent is amenable not only to the chlorination of nitrogen-containing heterocycles but also to selected classes of arenes, BODIPY dyes, and pharmaceuticals. In addition, the advantages, such as easy preparation and recyclable, air- and moisture-stable, in combination with the success in a gram-scale experiment grant this reagent great potential for industrial application. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Formula: C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Formula: C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Molecular design and preparation of 2-aminothiazole sulfanilamide oximes as membrane active antibacterial agents for drug resistant Acinetobacter baumannii》 was written by Wang, Juan; Zhang, Peng-Li; Ansari, Mohammad Fawad; Li, Shuo; Zhou, Cheng-He. Related Products of 3934-20-1 And the article was included in Bioorganic Chemistry in 2021. The article conveys some information:

A series of 2-aminothiazole sulfanilamide oximes were developed as new membrane active antibacterial agents to conquer the microbial infection. Benzoyl derivative 10c was preponderant for the treatment of drug-resistant A. baumannii infection in contrast to norfloxacin and exerted excellent biocompatibility against mammalian cells including erythrocyte and LO2 cell line. Meanwhile, it had ability to eradicate established biofilm to alleviate the resistance burden. Mechanism investigation elucidated that compound 10c was able to disturb the membrane effectively and inhibit lactic dehydrogenase, which led to cytoplasmic content leakage. The cellular redox homeostasis was interfered via the production of reactive oxygen and nitrogen species (RONS), which further contributed to respiratory pathway inactivation and reduction of GSH activity. This work indicated that 2-aminothiazole sulfanilamide oximes could be a promising start for the exploitation of novel antibacterial agents against pathogens. In addition to this study using 2,4-Dichloropyrimidine, there are many other studies that have used 2,4-Dichloropyrimidine(cas: 3934-20-1Related Products of 3934-20-1) was used in this study.

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Related Products of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Doll, Julianna S.; Eichelmann, Robert; Hertwig, Leif E.; Bender, Thilo; Kohler, Vincenz J.; Bill, Eckhard; Wadepohl, Hubert; Rosca, Dragos-Adrian published their research in ACS Catalysis in 2021. The article was titled 《Iron-Catalyzed Trimerization of Terminal Alkynes Enabled by Pyrimidinediimine Ligands: A Regioselective Method for the Synthesis of 1,3,5-Substituted Arenes》.Name: 2,4,6-Trichloropyrimidine The article contains the following contents:

The development of pyrimidine-based analogs of the well-known pyridinediimine (PDI) iron complexes e.g., I enables access to a functional-group-tolerant methodol. for the catalytic trimerization of terminal aliphatic alkynes RCC (R = 4-fluorophenyl, Bu, cyclopropyl, thiophen-2-yl, etc.). Remarkably, in contrast to established alkyne trimerization protocols, the 1,3,5-substituted arenes 1,3,5-R3C6H3 are the main reaction products. Preliminary mechanistic investigations suggest that the enhanced π-acidity of the pyrimidine ring, combined with the hemilability of the imine groups coordinated to the iron center, facilitates this transformation. The entry point in the catalytic cycle is an isolable iron dinitrogen complex. The catalytic reaction proceeds via a 1,3-substituted metallacycle, which explains the observed 1,3,5-regioselectivity. Such a metallacycle could be isolated and represents a rare 1,3-substituted ferracycle obtained through alkyne cycloaddition In the experimental materials used by the author, we found 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Formula: C6H3Cl2N3In 2014 ,《Synthesis and biological evaluation of substituted 2-anilino-7H-pyrrolopyrimidines as PDK1 inhibitors》 appeared in Tetrahedron. The author of the article were O’Brien, Nathan J.; Brzozowski, Martin; Wilson, David J. D.; Deady, Leslie W.; Abbott, Belinda M.. The article conveys some information:

An efficient and scalable route for a series of novel substituted 2-aniline-7H-pyrrolopyrimidine compounds as potential inhibitors of PDK1, an important regulator of the PI3K/Akt pathway that is dysregulated in many cancers, was developed and is described. The synthetic strategy was designed around a Suzuki coupling and Buchwald-Hartwig cross-coupling of a boronate fragment and various customized aniline derivatives sequentially with 2,4-dichloro-7-tosyl-7H-pyrrolopyrimidine. All fragments were constructed sep. and cross-coupled to provide access to a range of novel compounds Biol. evaluation of these was undertaken, with modest inhibition observed The synthesis of the target compounds was achieved using N-[3-amino-5-[2-oxo-2-[[2-(1-piperidinyl)ethyl]amino]ethyl]phenyl]-1-pyrrolidinecarboxamide, 3-amino-N-[2-(1-piperidinyl)ethyl]benzeneacetamide, 3-amino-N-[2-(1-piperidinyl)ethyl]benzamide and 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-Pyrrolo[2,3-d]pyrimidine as key intermediates.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Formula: C6H3Cl2N3) was used in this study.

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Formula: C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Oxidation of 2,4-disubstituted pyrimidines with organic peracids》 was written by Yamanaka, Hiroshi; Ogawa, Shigeru; Sakamoto, Takao. Application of 14001-60-6 And the article was included in Heterocycles on April 1 ,1981. The article conveys some information:

Reaction of 4,6-disubstituted pyrimidines with H2O2 in glacial HOAc gave the corresponding mono N-oxides. However, oxidation of pyrimidine derivatives in which the 6-position is unsubstituted gave both mono N-oxides and ring contracted 2,4-disubstituted imidazoles. In addition to this study using 2-Methoxy-4-methylpyrimidine, there are many other studies that have used 2-Methoxy-4-methylpyrimidine(cas: 14001-60-6Application of 14001-60-6) was used in this study.

2-Methoxy-4-methylpyrimidine(cas: 14001-60-6) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Application of 14001-60-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Viswanathan, Kishore; Frey, Kathleen M.; Scocchera, Eric W.; Martin, Brooke D.; Swain, P. Whitney III; Alverson, Jeremy B.; Priestley, Nigel D.; Anderson, Amy C.; Wright, Dennis L. published their research in PLoS One on February 29 ,2012. The article was titled 《Toward new therapeutics for skin and soft tissue infections: propargyl-linked antifolates are potent inhibitors of MRSA and Streptococcus pyogenes》.Category: pyrimidines The article contains the following contents:

Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 μg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clin. isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin. In the experiment, the researchers used 3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6Category: pyrimidines)

3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Category: pyrimidinesThey have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2014,Gehringer, Matthias; Forster, Michael; Pfaffenrot, Ellen; Bauer, Silke M.; Laufer, Stefan A. published 《Novel hinge-binding motifs for janus kinase 3 inhibitors: a comprehensive structure-activity relationship study on tofacitinib bioisosteres》.ChemMedChem published the findings.Related Products of 90213-66-4 The information in the text is summarized as follows:

The Janus kinases (JAKs) are a family of cytosolic tyrosine kinases crucially involved in cytokine signaling. JAKs have been demonstrated to be valid targets in the treatment of inflammatory and myeloproliferative disorders, and two inhibitors, tofacitinib and ruxolitinib, recently received their marketing authorization. Despite this success, selectivity within the JAK family remains a major issue. Both approved compounds share a common 7H-pyrrolo[2,3-d]pyrimidine hinge binding motif, and little is known about modifications tolerated at this heterocyclic core. In the current study, a library of tofacitinib bioisosteres was prepared and tested against JAK3. The compounds possessed the tofacitinib piperidinyl side chain, whereas the hinge binding motif was replaced by a variety of heterocycles mimicking its pharmacophore. In view of the promising expectations obtained from mol. modeling, most of the compounds proved to be poorly active. However, strategies for restoring activity within this series of novel chemotypes were discovered and crucial structure-activity relationships were deduced. The compounds presented may serve as starting point for developing novel JAK inhibitors and as a valuable training set for in silico models. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Related Products of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Han, Shuwen; Zhou, Wei; Zhuang, Chunlin; Chen, Fener published an article in Bioorganic Chemistry. The title of the article was 《Structure-Based design of Marine-derived Meridianin C derivatives as glycogen synthase kinase 3β inhibitors with improved oral bioavailability: From aminopyrimidyl-indoles to the sulfonyl analogues》.COA of Formula: C4H2Cl2N2 The author mentioned the following in the article:

Glycogen synthase kinase 3β (GSK-3β) has become an attractive target for the treatment of diabetes. Compound I is an indole-based GSK-3β inhibitor designed from the Meridianin C, a marine natural product (MNP) isolated from Aplidium meridianum. However, this compound has a moderate inhibitory activity toward GSK-3β (IC50 = 24.4 μM), moderate glucose uptake (38%), and especially, a low oral bioavailability (F = 11.4%). In the present study, applying the structure-based design strategy, a series of derivatives modified on the indole moiety were synthesized based on the lead compound I, followed by evaluating their cytotoxic activity, antihyperglycemic activity, and kinase inhibitory activity. Among this series, compound 6x with a sulfonyl group displayed the highest glucose uptake (83.5%) in muscle L6 cells, showing much higher inhibitory activity against GSK-3β (IC50 = 5.25 μM). Mol. docking indicated that compound 6x was properly inserted into the ATP-binding binding pocket of GSK-3β with a higher docking score (-8.145 kcal/mol) compared with that of compound I (-6.950 kcal/mol), interpreting the higher kinase inhibitory activity toward GSK-3β. Remarkably, compound 6x showed favorable drug-like properties, including significantly better oral bioavailability (F = 47.4%) and no two-week acute toxicity at a dose of 1g/kg. Our findings suggest that these MNP-derived sulfonyl indole derivatives could be used as lead compounds for the development of anti-hyperglycemic drugs. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1COA of Formula: C4H2Cl2N2)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.COA of Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia