Day: October 17, 2022

Application of 1353553-07-7On October 1, 2020 ,《Design, synthesis and antitumor activity of novel thiophene-pyrimidine derivatives as EGFR inhibitors overcoming T790M and L858R/T790M mutations》 was published in European Journal of Medicinal Chemistry. The article was written by Xiao, Zhen; Zhou, Zhihui; Chu, Cilong; Zhang, Qian; Zhou, Lingjia; Yang, Zunhua; Li, Xin; Yu, Liying; Zheng, Pengwu; Xu, Shan; Zhu, Wufu. The article contains the following contents:

Five series of novel thiophene-pyrimidine derivatives have been synthesized and tested for their anti-proliferative activity against several cancer cell lines in which EGF is highly expressed. Most of the target compounds showed excellent activity against one or more cancer cell lines. The most promising compound I, of which IC50 values on of cell lines A549 and A431 (4.34 ± 0.60μM and 3.79 ± 0.57μM) were similar to the lead compound Olmutinib, showed strong activity and selectivity to EGFRT790M and EGFRT790M/L858R. Inhibition data of human normal hepatoma cell line LO2 indicated that most target compounds were less toxic to normal cells and had selective inhibitory effects on cancer cells. In addition, the structure-activity relationship was analyzed and the mechanism of apoptosis induced by the compound I was studied. The results showed that compound I induced late apoptosis of A431 cancer cells in a dose-dependent manner. The results came from multiple reactions, including the reaction of 2-Chloro-4-(3-nitrophenoxy)thieno[3,2-d]pyrimidine(cas: 1353553-07-7Application of 1353553-07-7)

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.Application of 1353553-07-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Hotra, Adam; Ragunathan, Priya; Ng, Pearly Shuyi; Seankongsuk, Pattarakiat; Harikishore, Amaravadhi; Sarathy, Jickky Palmae; Saw, Wuan-Geok; Lakshmanan, Umayal; Sae-Lao, Patcharaporn; Kalia, Nitin Pal; Shin, Joon; Kalyanasundaram, Revathy; Anbarasu, Sivaraj; Parthasarathy, Krupakar; Pradeep, Chaudhari Namrata; Makhija, Harshyaa; Droege, Peter; Poulsen, Anders; Tan, Jocelyn Hui Ling; Pethe, Kevin; Dick, Thomas; Bates, Roderick W.; Grueber, Gerhard published an article in Angewandte Chemie, International Edition. The title of the article was 《Discovery of a Novel Mycobacterial F-ATP Synthase Inhibitor and its Potency in Combination with Diarylquinolines》.Product Details of 86443-51-8 The author mentioned the following in the article:

The F1FO-ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clin. target. A mycobacterium-specific loop of the enzyme’s rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1 (I), that targets this γ subunit loop. Biochem. and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug- as well as bedaquiline-resistant strains. Chem. efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogs with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogs showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti-tuberculosis F-ATP synthase inhibitors.2-Chloro-N-ethylpyrimidin-4-amine(cas: 86443-51-8Product Details of 86443-51-8) was used in this study.

2-Chloro-N-ethylpyrimidin-4-amine(cas: 86443-51-8) belongs to anime. In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (NH3), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines).Product Details of 86443-51-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sutherlin, Daniel P.; Sampath, Deepak; Berry, Megan; Castanedo, Georgette; Chang, Zhigang; Chuckowree, Irina; Dotson, Jenna; Folkes, Adrian; Friedman, Lori; Goldsmith, Richard; Heffron, Tim; Lee, Leslie; Lesnick, John; Lewis, Cristina; Mathieu, Simon; Nonomiya, Jim; Olivero, Alan; Pang, Jodie; Prior, Wei Wei; Salphati, Laurent; Sideris, Steve; Tian, Qingping; Tsui, Vickie; Wan, Nan Chi; Wang, Shumei; Wiesmann, Christian; Wong, Susan; Zhu, Bing-Yan published an article on February 11 ,2010. The article was titled 《Discovery of (Thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors for the Treatment of Cancer》, and you may find the article in Journal of Medicinal Chemistry.Application In Synthesis of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine The information in the text is summarized as follows:

The PI3K/AKT/mTOR pathway has been shown to play an important role in cancer. Starting with compounds I and 2 (GDC-0941) as templates, (thienopyrimidin-2-yl)aminopyrimidines were discovered as potent inhibitors of PI3K or both PI3K and mTOR. Structural information derived from PI3Kγ-ligand cocrystal structures of I and 2 were used to design inhibitors that maintained potency for PI3K yet improved metabolic stability and oral bioavailability relative to I. The addition of a single Me group to the optimized 5 resulted in 21, which had significantly reduced potency for mTOR. The lead compounds 5 (GNE-493) and 21 (GNE-490) have good pharmacokinetic (PK) parameters, are highly selective, demonstrate knock down of pathway markers in vivo, and are efficacious in xenograft models where the PI3K pathway is deregulated. Both compounds were compared in a PI3Kα mutated MCF7.1 xenograft model and were found to have equivalent efficacy when normalized for exposure. In the experiment, the researchers used many compounds, for example, 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2Application In Synthesis of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine)

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2) 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. Application In Synthesis of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Synthesis of pyrimido[4,5-d]pyrimidines. An unusual rearrangement of 2-aminopyrimido[4,5-d]pyrimidin-5(6H)-one into 2-amino-4,6-dichloro-1,3,5-triazine》 were Stanovnik, B.; Koren, B.; Steblaj, M.; Tisler, M.; Zmitek, J.. And the article was published in Vestnik Slovenskega Kemijskega Drustva in 1982. Electric Literature of C7H10N4O2 The author mentioned the following in the article:

Pyrimidopyrimidine I (R = NH2, R1 = H) was obtained by treating 5-carbamoyl-2,4-pyrimidinediamine (II) with HC(OEt)3 or CH(NHCHO)3. I (R = N:CMeOEt, R1 = Me) was obtained from II and MeC(OEt)3. Treatment of I (R = NH2, R1 = H) with POCl3 gave the triazine III. In the experiment, the researchers used Ethyl 2,4-diaminopyrimidine-5-carboxylate(cas: 15400-54-1Electric Literature of C7H10N4O2)

Ethyl 2,4-diaminopyrimidine-5-carboxylate(cas: 15400-54-1) belongs to anime. Acylation is one of the most important reactions of primary and secondary amines; a hydrogen atom is replaced by an acyl group (a group derived from an acid, such as RCOOH or RSO3H, by removal of ―OH, such as RC(=O)―, RS(O)2―, and so on). Reagents may be acid chlorides (RCOC1, RSO2C1), anhydrides ((RCO)2O), or even esters (RCOOR′); the products are amides of the corresponding acids.Electric Literature of C7H10N4O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2010,Khoje, Abhijit Datta; Kulendrn, Aisvareya; Charnock, Colin; Wan, Baojie; Franzblau, Scott; Gundersen, Lise-Lotte published 《Synthesis of non-purine analogs of 6-aryl-9-benzylpurines, and their antimycobacterial activities: Compounds modified in the imidazole ring》.Bioorganic & Medicinal Chemistry published the findings.Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The information in the text is summarized as follows:

Purine analogs modified in the five-membered ring have been synthesized and examined for antibacterial activity against Mycobacterium tuberculosis H37Rv in vitro employing the microplate alamar blue assay (MABA). The 9-deaza analogs were only found to be weak inhibitors, but the 8-aza-, 7-deaza- and 8-aza-7-deazapurine analogs studied displayed excellent antimycobacterial activities, some even substantially better than the parent purine. In the 7-deazapurine series, MIC values between 0.08 and 0.35 μM, values comparable or better than the reference drugs used in the study (MIC rifampicin 0.09 μM, MIC isoniazid 0.28 μM and MIC PA-824 0.44 μM). The five most active compounds were also examined against a panel of drug-resistant Mtb strain, and they all retained their activity. The compounds examined were significantly less active against M. tuberculosis in a state of non-replicating persistence (NRP). MIC in the low-oxygen-recovery assay (LORA) ≥60 μM. The 7-deazapurines were somewhat more toxic towards mammalian cells, but still the selectivity indexes were excellent. The non-purine analogs exhibit a selective antimycobacterial activity. They were essentially inactive against Staphylococcus aureus and Escherichia coli. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Quality Control 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. 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. Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Bruening, Fabian; Lovelle, Lucie E. published 《Highly regioselective organocatalytic SNAr amination of 2,4-dichloropyrimidine and related heteroaryl chlorides》.European Journal of Organic Chemistry published the findings.Safety of 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

A highly efficient and regioselective method for the SNAr amination of 2,4-dichloropyrimidine with oxazolidin-2-one and related weakly nucleophilic amines, using sodium sulfinate and tetrabutylammonium bromide as catalysts, is disclosed. This strategy facilitates the synthesis of various aminopyrimidines, e.g., I, in a regio- and chemoselective manner. This approach was successfully used for the amination of various activated N-heteroaromatic substrates. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Safety of 2,4,6-Trichloropyrimidine)

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.Safety of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Bioorganic & Medicinal Chemistry Letters included an article by Huang, Boshi; Liu, Xinhao; Tian, Ye; Kang, Dongwei; Zhou, Zhongxia; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. Application of 90213-66-4. The article was titled 《First discovery of a potential carbonate prodrug of NNRTI drug candidate RDEA427 with submicromolar inhibitory activity against HIV-1 K103N/Y181C double mutant strain》. The information in the text is summarized as follows:

In the present work, we described the synthesis, antiviral profiles and metabolic stability in human plasma of compound 6, a potential carbonate prodrug of HIV-1 NNRTI drug candidate RDEA427. Compound 6 was found to inhibit the wild-type (WT) and K103N/Y181C double mutant HIV-1 strains at nano- and submicromolar concentrations, resp. Moreover, it displayed potent HIV-1 reverse transcriptase inhibitory activity (IC50=0.264μM). Further stability test in human plasma showed that 6 could release its active form RDEA427 in a linearly time-independent manner, possibly acting as a potential prodrug. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Application of 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. Application of 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

In 2018,European Journal of Organic Chemistry included an article by Bruening, Fabian; Katayev, Dmitry; Togni, Antonio. Synthetic Route of C4HCl3N2. The article was titled 《Facile and Efficient Synthesis of 3-Pyrimidinyl Oxindoles by Phase-Transfer-Catalyzed Regioselective Nucleophilic Aromatic Substitution》. The information in the text is summarized as follows:

Phase-transfer-catalyzed regioselective nucleophilic aromatic substitution of 2,4-dichloropyrimidines with N-Boc-protected 3-substituted oxindoles is reported. The reaction allows the formation of unsym. all- carbon quaternary centers in the benzylic position of heteroaromatic scaffolds and proceeds with high chem. yield and excellent functional-group tolerance. Various activated heteroaryl chlorides including dichloropyridazine and activated chloropyridines can also be reacted under the reaction conditions. The experimental part of the paper was very detailed, including the reaction process of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Synthetic Route of C4HCl3N2)

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.Synthetic Route of C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Journal of the American Chemical Society included an article by Pisa, Rudolf; Cupido, Tommaso; Kapoor, Tarun M.. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine. The article was titled 《Designing Allele-Specific Inhibitors of Spastin, a Microtubule-Severing AAA Protein》. The information in the text is summarized as follows:

The bump-hole approach is a powerful chem. biol. strategy to specifically probe the functions of closely related proteins. However, for many protein families, such as the ATPases associated with diverse cellular activities (AAA), we lack structural data for inhibitor-protein complexes to design allele-specific chem. probes. Here we report the X-ray structure of a pyrazolylaminoquinazoline-based inhibitor bound to spastin, a microtubule-severing AAA protein, and characterize the residues involved in inhibitor binding. We show that an inhibitor analog with a single-atom hydrogen-to-fluorine modification can selectively target a spastin allele with an engineered cysteine mutation in its active site. We also report an X-ray structure of the fluoro analog bound to the spastin mutant. Furthermore, analyses of other mutant alleles suggest how the stereoelectronics of the fluorine-cysteine interaction, rather than sterics alone, contribute to the inhibitor-allele selectivity. This approach could be used to design allele-specific probes for studying cellular functions of spastin isoforms. Our data also suggest how tuning stereoelectronics can lead to specific inhibitor-allele pairs for the AAA superfamily. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Name: 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. 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. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,ACS Applied Materials & Interfaces included an article by Shafikov, Marsel Z.; Daniels, Ruth; Pander, Piotr; Dias, Fernando B.; Williams, J. A. Gareth; Kozhevnikov, Valery N.. Application In Synthesis of 4,6-Dichloropyrimidine. The article was titled 《Dinuclear Design of a Pt(II) Complex Affording Highly Efficient Red Emission: Photophysical Properties and Application in Solution-Processible OLEDs》. The information in the text is summarized as follows:

The light-emitting efficiency of luminescent materials is invariably compromised on moving to the red and near-IR regions of the spectrum due to the transfer of electronic excited-state energy into vibrations. The authors describe how this undesirable energy gap law can be sidestepped for phosphorescent organometallic emitters through the design of a mol. emitter that incorporates two Pt(II) centers. The dinuclear cyclometalated complex of a substituted 4,6-bis(2-thienyl)pyrimidine emits very brightly in the red region of the spectrum (λmax = 610 nm, Φ = 0.85 in deoxygenated CH2Cl2 at 300 K). The lowest-energy absorption band is extraordinarily intense for a cyclometalated metal complex: at λ = 500 nm, ε = 53,800 M-1 cm-1. The very high efficiency of emission achieved can be traced to an unusually high rate constant for the T1 → S0 phosphorescence process, allowing it to compete effectively with nonradiative vibrational decay. The high radiative rate constant correlates with an unusually large zero-field splitting of the triplet state, which is 40 cm-1 by variable-temperature time-resolved spectroscopy over the range 1.7 < T < 120 K. The compound was successfully tested as a red phosphor in an organic light-emitting diode prepared by solution processing. The results highlight a potentially attractive way to develop highly efficient red and NIR-emitting devices through the use of multinuclear complexes. In the experimental materials used by the author, we found 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