Tag: 100-200

Jin, Xin; Piao, Hu-Ri; Pannecouque, Christophe; De Clercq, Erik; Zhuang, Chunlin; Chen, Fen-Er published an article in 2021. The article was titled 《Design of the naphthyl-diarylpyrimidines as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) via structure-based extension into the entrance channel》, and you may find the article in European Journal of Medicinal Chemistry.Application of 3764-01-0 The information in the text is summarized as follows:

A series of novel naphthyl-diarylpyrimidine (DAPY) derivatives were designed and synthesized to explore the entrance channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating different flexible side chains at the C-6 position. The biol. evaluation results showed that all analogs possessed promising HIV-1 inhibitory activity at the nanomolar concentration range. Three compounds (7, 9 and 39) displayed excellent potency against WT HIV-1 strain with EC50 values ranging from 5 to 10 nM and high selectivity indexes (SI = 3504, 30488 and 22846, resp.), which were higher than for nevirapine and comparable to the values for etravirine. The RT inhibition activity, preliminary structure-activity relationship and mol. docking study showed that the side chain at the C-6 position of the DAPYs occupied the entrance channel and significantly influenced anti-HIV activity and selectivity. Addnl., the physicochem. properties were investigated to evaluate the drug-like features, which indicated that introducing various substituents on the pyrimidine ring can improve solubility In the experiment, the researchers used many compounds, for example, 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) 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.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Feng, Da; Zuo, Xiaofang; Jing, Lanlan; Chen, Chin-Ho; Olotu, Fisayo A.; Lin, Hao; Soliman, Mahmoud; De Clercq, Erik; Pannecouque, Christophe; Lee, Kuo-Hsiung; Kang, Dongwei; Liu, Xinyong; Zhan, Peng published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Design, synthesis, and evaluation of “”dual-site””-binding diarylpyrimidines targeting both NNIBP and the NNRTI adjacent site of the HIV-1 reverse transcriptase》.Product Details of 3934-20-1 The article contains the following contents:

To improve the drug-resistance profiles of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a novel series of “”dual-site”” binding diarylpyrimidine (DAPY) derivatives I [R1 = H, cyclopropyl, propargyl, etc.] and II [X = 1-R2-piperidin-4-yl, 1-R2-piperidin-4-ylmethyl, 1-R2-pyrrolidin-3-yl; R2 = methylsulfonyl, trifluoromethylsulfonyl, trifluoromethylcarbonyl, etc.] targeting both the NNRTI adjacent site and NNRTIs binding pocket (NNIBP) were designed, synthesized and evaluated for their anti-HIV potency in TZM-bl and MT-4 cells. Eight compounds I and II exhibited moderate to excellent potencies in inhibiting wild-type (WT) HIV-1 replication with EC50 values ranging from 2.45 nM to 5.36 nM, and I [R1 = propargylamino] (EC50 = 2.45 nM) proved to be the most promising inhibitor. Of note, I [R1 = propargylamino] exhibited potent activity against the single mutant strain E138K (EC50 = 10.6 nM), being comparable with ETR (EC50 = 9.80 nM) and 3.5-fold more potent than that of morpholino pyrimidine compound (EC50 = 37.3 nM). Moreover, I [R1 = propargylamino] acted as a classical NNRTI with high affinity for WT HIV-1 RT (IC50 = 0.0589μM). The detailed structure-activity relationships (SARs) of the representative compounds were also determined, and further supported by mol. dynamics simulation. Overall, the “”dual-site””-binding NNRTIs have significant prospects and pave the way for the next round of rational design of potent anti-HIV-1 agents. In the experiment, the researchers used 2,4-Dichloropyrimidine(cas: 3934-20-1Product Details of 3934-20-1)

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.Product Details of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Structure-Activity Relationship Study of Covalent Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors》 was written by Manz, Theresa D.; Sivakumaren, Sindhu C.; Yasgar, Adam; Hall, Matthew D.; Davis, Mindy I.; Seo, Hyuk-Soo; Card, Joseph D.; Ficarro, Scott B.; Shim, Hyeseok; Marto, Jarrod A.; Dhe-Paganon, Sirano; Sasaki, Atsuo T.; Boxer, Matthew B.; Simeonov, Anton; Cantley, Lewis C.; Shen, Min; Zhang, Tinghu; Ferguson, Fleur M.; Gray, Nathanael S.. Recommanded Product: 1193-21-1 And the article was included in ACS Medicinal Chemistry Letters in 2020. The article conveys some information:

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are important mol. players in a variety of diseases, such as cancer. Currently available PI5P4K inhibitors are reversible small mols., which may lack selectivity and sufficient cellular on-target activity. In this study, we present a new class of covalent pan-PI5P4K inhibitors with potent biochem. and cellular activity. Our designs are based on THZ-P1-2, a covalent PI5P4K inhibitor previously developed in our laboratory Here, we report further structure-guided optimization and structure-activity relationship (SAR) study of this scaffold, resulting in compound 30(I), which retained biochem. and cellular potency, while demonstrating a significantly improved selectivity profile. Furthermore, we confirm that the inhibitors show efficient binding affinity in the context of HEK 293T cells using isothermal CETSA methods. Taken together, I represents a highly selective pan-PI5P4K covalent lead mol. In the experiment, the researchers used 4,6-Dichloropyrimidine(cas: 1193-21-1Recommanded Product: 1193-21-1)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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.Recommanded Product: 1193-21-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors》 was written by Shu, Lei; Chen, Chengjuan; Huan, Xueting; Huang, Hao; Wang, Manman; Zhang, Jianqiu; Yan, Yile; Liu, Jianming; Zhang, Tiantai; Zhang, Dayong. Application In Synthesis of 4,6-Dichloropyrimidine And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

In this work, poorly selective compounds based on 4- or 6-phenyl-pyrimidine derivatives I and II [R = H, prop-2-enamidyl, but-2-enamidyl, 2-cyanoacetamidyl; R1 = 1-methyl-1H-pyrazol-4-yl, 1-(2-methoxyethyl)-1H-pyrazol-4-yl, 4-(4-morpholinyl)phenyl, etc.; R2 = H, prop-2-enamidyl, but-2-enamidyl, 2-cyanoacetamidyl] have been improved to highly potent and selective compounds by designing a covalent binding tether, which attaches to the unique cysteine (Cys909) residue in JAK3. Compound II [R = prop-2-enamidyl; R1 = 4-(4-morpholinyl)phenyl, R2 = H (A)] exhibited potent JAK3 inhibitory activity (IC50 = 1.7 nM) with an excellent selectivity profile when compared to the other JAK isoforms (>588-fold). In a cellular assay, compound (A) strongly inhibited JAK3-dependent signaling and T cell proliferation. Moreover, in vivo data revealed that compound (A) significantly suppressed oxazolone (OXZ)-induced delayed hypersensitivity responses in Balb/c mice. Compound (A) also displayed decent pharmacokinetic properties and was suitable for in vivo use. Taken together, these results indicated that compound (A) may be a promising tool compound as a selective JAK3 inhibitor for treating autoimmune diseases. The experimental process involved the reaction of 4,6-Dichloropyrimidine(cas: 1193-21-1Application In Synthesis of 4,6-Dichloropyrimidine)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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.Application In Synthesis of 4,6-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design and Discovery of an Orally Efficacious Spiroindolinone-Based Tankyrase Inhibitor for the Treatment of Colon Cancer》 was written by Shirai, Fumiyuki; Mizutani, Anna; Yashiroda, Yoko; Tsumura, Takeshi; Kano, Yuko; Muramatsu, Yukiko; Chikada, Tsubasa; Yuki, Hitomi; Niwa, Hideaki; Sato, Shin; Washizuka, Kenichi; Koda, Yasuko; Mazaki, Yui; Jang, Myung-Kyu; Yoshida, Haruka; Nagamori, Akiko; Okue, Masayuki; Watanabe, Takashi; Kitamura, Kouichi; Shitara, Eiki; Honma, Teruki; Umehara, Takashi; Shirouzu, Mikako; Fukami, Takehiro; Seimiya, Hiroyuki; Yoshida, Minoru; Koyama, Hiroo. Category: pyrimidines And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:

Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymic activities attenuates the Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported the discovery of RK-287107, a spiroindoline-based, highly selective, potent tankyrase inhibitor. Herein we describe the optimization process of RK-287107 leading to RK-582, which exhibits a markedly improved robust tumor growth inhibition in a COLO-320DM mouse xenograft model when orally administered. In addition to the dose-dependent elevation and attenuation of the levels of biomarkers AXIN2 and β-catenin, resp., results of the TCF reporter and cell proliferation studies on COLO-320DM are discussed. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Category: pyrimidines)

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. Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Journal of Organic Chemistry included an article by Bhujabal, Yuvraj B.; Vadagaonkar, Kamlesh S.; Gholap, Aniket; Sanghvi, Yogesh S.; Dandela, Rambabu; Kapdi, Anant R.. Computed Properties of C4H2Cl2N2. The article was titled 《HFIP Promoted Low Temperature SNAr of Chloroheteroarenes Using Thiols and Amines》. The information in the text is summarized as follows:

A highly efficient and an unprecedented HFIP promoted low temperature aromatic nucleophilic substitutions of chloroheteroarenes has been performed using thiols and (secondary) amines under base-free and metal-free conditions. The developed protocol also provides excellent regio-control for the selective functionalization of dichloroheteroarenes, while the utility of the protocol was demonstrated by the modification of a com. available drug Ceritinib. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloropyrimidine(cas: 3934-20-1Computed Properties of C4H2Cl2N2)

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.Computed Properties of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Korchagin, D. V.; Aldoshin, S. M.; Chernyak, A. V.; Chapyshev, S. V. published 《Molecular and crystal structure of 2,4,6-triazidopyrimidine and its chloro-substituted derivative》.Journal of Structural Chemistry published the findings.Application of 3764-01-0 The information in the text is summarized as follows:

Single-crystal X-ray diffraction combined with quantum-chem. calculations and 15N NMR spectroscopy were used to investigate the mol. and crystal structures of the high-energy 2,4,6-triazidopyrimidine and 2,4,6-triazido-5-chloropyrimidine and analyzed the dependence of the structural parameters of their azido groups on the position in the pyrimidine ring. In the experimental materials used by the author, we found 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0)

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.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2016,Trist, Iuni M. L.; Nannetti, Giulio; Tintori, Cristina; Fallacara, Anna Lucia; Deodato, Davide; Mercorelli, Beatrice; Palu, Giorgio; Wijtmans, Maikel; Gospodova, Tzveta; Edink, Ewald; Verheij, Mark; de Esch, Iwan; Viteva, Lilia; Loregian, Arianna; Botta, Maurizio published 《4,6-Diphenylpyridines as Promising Novel Anti-Influenza Agents Targeting the PA-PB1 Protein-Protein Interaction: Structure-Activity Relationships Exploration with the Aid of Molecular Modeling》.Journal of Medicinal Chemistry published the findings.HPLC of Formula: 3764-01-0 The information in the text is summarized as follows:

Influenza is an infectious disease that represents an important public health burden, with high impact on the global morbidity, mortality, and economy. The poor protection and the need of annual updating of the anti-influenza vaccine, added to the rapid emergence of viral strains resistant to current therapy make the need for antiviral drugs with novel mechanisms of action compelling. In this regard, the viral RNA polymerase is an attractive target that allows the design of selective compounds with reduced risk of resistance. In previous studies we showed that the inhibition of the polymerase acidic protein-basic protein 1 (PA-PB1) interaction is a promising strategy for the development of anti-influenza agents. Starting from the previously identified 3-cyano-4,6-diphenyl-pyridines, we chem. modified this scaffold and explored its structure-activity relationships. Noncytotoxic compounds with both the ability of disrupting the PA-PB1 interaction and antiviral activity were identified, and their mechanism of target binding was clarified with mol. modeling simulations. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0HPLC of Formula: 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) 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.HPLC of Formula: 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2015,Delia, Thomas J.; Hood, Robin J. published 《Bromination of Pyrimidines: A Simple Inexpensive Method》.Australian Journal of Chemistry published the findings.Recommanded Product: 3764-01-0 The information in the text is summarized as follows:

Although the introduction of halogens into the pyrimidine ring has been accomplished numerous times, the methods usually involve either specialized reagents or very aggressive conditions. This communication paper describes the introduction of bromine into position 5 of the pyrimidine ring using common inorganic salts at room temperature An evaluation of the substituents required for successful reaction is provided. In the part of experimental materials, we found many familiar compounds, such as 2,4,6-Trichloropyrimidine(cas: 3764-01-0Recommanded Product: 3764-01-0)

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.Recommanded Product: 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2014,Odingo, Joshua; O’Malley, Theresa; Kesicki, Edward A.; Alling, Torey; Bailey, Mai Ann; Early, Julie; Ollinger, Juliane; Dalai, Suryakanta; Kumar, Naresh; Singh, Ravindra Vikram; Hipskind, Philip A.; Cramer, Jeffrey W.; Ioerger, Thomas; Sacchettini, James; Vickers, Richard; Parish, Tanya published 《Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents》.Bioorganic & Medicinal Chemistry published the findings.HPLC of Formula: 90213-66-4 The information in the text is summarized as follows:

The 2,4-diaminoquinazoline class of compounds has previously been identified as an effective inhibitor of Mycobacterium tuberculosis growth. The authors conducted an extensive evaluation of the series for its potential as a lead candidate for tuberculosis drug discovery. Three segments of the representative mol. N-(4-fluorobenzyl)-2-(piperidin-1-yl)quinazolin-4-amine were examined systematically to explore structure-activity relationships influencing potency. The authors determined that the benzylic amine at the 4-position, the piperidine at 2-position and the N-1 (but not N-3) are key activity determinants. The 3-deaza analog retained similar activity to the parent mol. Biol. activity was not dependent on iron or carbon source availability. The authors demonstrated through pharmacokinetic studies in rats that good in vivo compound exposure is achievable. A representative compound demonstrated bactericidal activity against both replicating and nonreplicating M. tuberculosis. The authors isolated and sequenced M. tuberculosis mutants resistant to this compound and observed mutations in Rv3161c, a gene predicted to encode a dioxygenase, suggesting that the compound may act as a prodrug. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4HPLC of Formula: 90213-66-4)

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. HPLC of Formula: 90213-66-4They 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