Day: October 17, 2022

In 2022,Wu, Tianxiao; Qin, Qiaohua; Liu, Nian; Zhang, Chu; Lv, Ruicheng; Yin, Wenbo; Sun, Yin; Sun, Yixiang; Wang, Ruifeng; Zhao, Dongmei; Cheng, Maosheng published an article in European Journal of Medicinal Chemistry. The title of the article was 《Rational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold》.Recommanded Product: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound I was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Addnl., compound I induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot anal. revealed that compound I inhibited the phosphorylation of TRK to block downstream pathways. Compound I also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, resp. Pharmacokinetic studies indicated that the oral bioavailability of compound I is 17.4%. These results demonstrate that compound I could serve as a novel lead compound for overcoming NTRK-fusion cancers. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Recommanded Product: 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. Recommanded Product: 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 2022,Hua, Yi; Fang, Xiaobao; Xing, Guomeng; Xu, Yuan; Liang, Li; Deng, Chenglong; Dai, Xiaowen; Liu, Haichun; Lu, Tao; Zhang, Yanmin; Chen, Yadong published an article in Journal of Chemical Information and Modeling. The title of the article was 《Effective reaction-based de novo strategy for kinase targets: A case study on MERTK inhibitors》.Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

Reaction-based de novo design is the computational generation of novel mol. structures by linking building blocks using reaction vectors derived from chem. knowledge. In this work, we first adopted a recurrent neural network (RNN) model to generate three groups of building blocks with different functional groups and then constructed an in silico target-focused combinatorial library based on chem. reaction rules. Mer tyrosine kinase (MERTK) was used as a study case. Combined with a scaffold enrichment anal., 15 novel MERTK inhibitors covering four scaffolds were achieved. Among them, compound 5a obtained an IC50 value of 53.4 nM against MERTK without any further optimization. The efficiency of hit identification could be significantly improved by shrinking the compound library with the fragment iterative optimization strategy and enriching the dominant scaffold in the hinge region. We hope that this strategy can provide new insights for accelerating the drug discovery process. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Application In Synthesis 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. Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Product Details of 3934-20-1In 2020 ,《Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Sui, Yan-Fei; Li, Di; Wang, Juan; Bheemanaboina, Rammohan R. Yadav; Ansari, Mohammad Fawad; Gan, Lin-Ling; Zhou, Cheng-He. The article conveys some information:

This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target mols. were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 μg/mL. The active mol. 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramol. complex, which might be responsible for its antimicrobial action. The further investigation showed that this mol. could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force. In the experimental materials used by the author, we found 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 chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Product Details of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Name: 2,4,6-TrichloropyrimidineIn 2016 ,《Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Hu, Jianping; Wang, Xin; Chen, Lin; Huang, Min; Tang, Wei; Zuo, Jianping; Liu, Yu-Chih; Shi, Zhe; Liu, Rongfeng; Shen, Jingkang; Xiong, Bing. The article conveys some information:

The histone methylation on lysine residues is one of the most studied posttranslational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure-activity relationship of this series of compounds Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development. To further elaborate the structure-activity relationship of selective JMJD3 inhibitors and to explore the novel chelating groups for Fe(II) ion, the authors initialized a medicinal chem. modification based on the GSK-J1 structure. Finally, the authors found that several compounds bearing different chelating groups showed similar activities with respect to GSK-J1 and excellent metabolic stability in liver microsomes. The Et ester prodrugs of these inhibitors also showed a better activity than GSK-J4 for inhibition of TNF-α production in LPS-stimulated murine macrophage cell line Raw 264.7 cells. Taking together, the current study not only discovered alternative potent JMJD3 inhibitors, but also can benefit other researchers to design new series of Jumonji demethylase inhibitors based on the identified chelating groups. The experimental process involved the reaction of 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. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2015 ,《Pyrimidinone Nicotinamide Mimetics as Selective Tankyrase and Wnt Pathway Inhibitors Suitable for in Vivo Pharmacology》 appeared in ACS Medicinal Chemistry Letters. The author of the article were Johannes, Jeffrey W.; Almeida, Lynsie; Barlaam, Bernard; Boriack-Sjodin, P. Ann; Casella, Robert; Croft, Rosemary A.; Dishington, Allan P.; Gingipalli, Lakshmaiah; Gu, Chungang; Hawkins, Janet L.; Holmes, Jane L.; Howard, Tina; Huang, Jian; Ioannidis, Stephanos; Kazmirski, Steven; Lamb, Michelle L.; McGuire, Thomas M.; Moore, Jane E.; Ogg, Derek; Patel, Anil; Pike, Kurt G.; Pontz, Timothy; Robb, Graeme R.; Su, Nancy; Wang, Haiyun; Wu, Xiaoyun; Zhang, Hai-Jun; Zhang, Yue; Zheng, Xiaolan; Wang, Tao. The article conveys some information:

The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis, and cancer. Germline mutations of several Wnt pathway components, such as Axin, APC, and ss-catenin, can lead to oncogenesis. Inhibition of the poly(ADP-ribose) polymerase (PARP) catalytic domain of the tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway via increased stabilization of Axin. In order to explore the consequences of tankyrase and Wnt pathway inhibition in preclin. models of cancer and its impact on normal tissue, the authors sought a small mol. inhibitor of TNKS1/2 with suitable physicochem. properties and pharmacokinetics for hypothesis testing in vivo. Starting from a 2-Ph quinazolinone hit I, the authors discovered the pyrrolopyrimidinone compound II (AZ6102), which is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. Moreover, compound II can be formulated well in a clin. relevant i.v. solution at 20 mg/mL, has demonstrated good pharmacokinetics in preclin. species, and shows low Caco2 efflux to avoid possible tumor resistance mechanisms. The results came from multiple reactions, including the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Application In Synthesis 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 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 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 3934-20-1In 2021 ,《Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design》 was published in European Journal of Medicinal Chemistry. The article was written by Wang, Linxiao; Zhang, Qian; Wang, Zhe; Zhu, Wufu; Tan, Ninghua. The article contains the following contents:

Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine I [X = C, C=O; Y = H, N(Me)2, N(Et)2] II [R = H, Me; R2 = pyrrolidin-1-yl, 1-piperidyl, morpholino, indolin-1-yl, 3,4-dihydro-1H-isoquinolin-2-yl] III and N-methylpicolinamide derivatives IV [R2 = pyrrolidin-1-yl, 1-piperidyl, morpholino, 3,4-dihydro-1H-isoquinolin-2-yl] substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds I, II, III, IV showed selectivity toward the A549 cell lines and the most promising compound IV [R2 = 1-piperidyl] could inhibit TAK1 kinase and NF-κB signaling pathway with the IC50 values of 0.58 and 0.84μM. Moreover, IV [R2 = 1-piperidyl] could induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound IV [R2 = 1-piperidyl] could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. The studies of docking, mol. dynamics, MM/PBSA and frequency anal. theor. supported the conclusions of the bioevaluation. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Related Products of 3934-20-1)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Related Products of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Decomposition of thiamine in alcohol solution. II》 was published in Chemical & Pharmaceutical Bulletin in 1974. These research results belong to Shimahara, Noboru; Asakawa, Hiroyuki; Kawamatsu, Yutaka; Hirano, Hiroshi. COA of Formula: C6H8ClN3 The article mentions the following:

Thiamine mononitrate I was decomposed in MeOH solution to produce the pentamer II and the thiazole III. II was converted to 9-amino-2,7,10-trimethyl-5H-dipyrimido[1,6-a:4′,5′-d]pyrimidine. Decomposition of thiamine monochloride in MeOH followed by AgNO3 gave II. II in aqueous solution reacted with acidic sodium sulfite to give 4-amino-2-methylpyrimidinyl-5-methanesulfonic acid. In the experiment, the researchers used many compounds, for example, 6-Chloro-2,5-dimethylpyrimidin-4-amine(cas: 18260-92-9COA of Formula: C6H8ClN3)

6-Chloro-2,5-dimethylpyrimidin-4-amine(cas: 18260-92-9) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.COA of Formula: C6H8ClN3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR》 was written by Heffron, Timothy P.; Ndubaku, Chudi O.; Salphati, Laurent; Alicke, Bruno; Cheong, Jonathan; Drobnick, Joy; Edgar, Kyle; Gould, Stephen E.; Lee, Leslie B.; Lesnick, John D.; Lewis, Cristina; Nonomiya, Jim; Pang, Jodie; Plise, Emile G.; Sideris, Steve; Wallin, Jeffrey; Wang, Lan; Zhang, Xiaolin; Olivero, Alan G.. Quality Control of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine And the article was included in ACS Medicinal Chemistry Letters on April 14 ,2016. The article conveys some information:

Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). The authors previously disclosed the successful approach to prospectively design potent and blood-brain barrier (BBB) penetrating PI3K inhibitors. The previously disclosed mols. were ultimately deemed not suitable for clin. development due to projected poor metabolic stability in humans. The authors, therefore, extended the studies to identify a BBB penetrating inhibitor of PI3K that was also projected to be metabolically stable in human. These efforts required identification of a distinct scaffold for PI3K inhibitors relative to the authors’ previous efforts and ultimately resulted in the identification of GDC-0084. The discovery and preclin. characterization of this mol. are described within. In addition to this study using 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine, there are many other studies that have used 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2Quality Control of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine) was used in this study.

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 derivatives also play an important role in drug development, either in concert with other compounds or on their own. Quality Control of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amineThey 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

《Triptycene based and nitrogen rich hyper cross linked polymers (TNHCPs) as efficient CO2 and iodine adsorbent》 was written by Hassan, Atikur; Goswami, Santu; Alam, Akhtar; Bera, Ranajit; Das, Neeladri. Application In Synthesis of 2,4-DichloropyrimidineThis research focused ontriptycene pyrazine copolymer crosslinked radioactive waste iodine adsorbent; carbon dioxide adsorption air pollution reusable recyclable. The article conveys some information:

Triptycene based polymeric networks are rapidly emerging as porous organic polymers (POPs) for efficient capture of small gas mols. Further, such triptycene based frameworks are also being explored as adsorbents for radioactive iodine. Herein, a group of three unique “”Triptycene based and Nitrogen-rich Hyper Crosslinked Polymers”” (TNHCPs) have been easily obtained via the well-known Friedel-Craft alkylation reactions of triptycene with six-membered N-rich heterocycles. In these TNHCPs, the presence of triptycene motifs yields contorted and rigid polymeric frameworks with plenty of micropores and ultramicropores. Further, the presence of N-rich heterocycles increases their efficiency to selectively capture carbon dioxide and adsorb iodine vapors as well as iodide ions from aqueous solutions Comparison with data in recent literature reveals that TNHCPs are better in these domains than several previously reported POPs in general and HCPs in particular. In the experiment, the researchers used 2,4-Dichloropyrimidine(cas: 3934-20-1Application In Synthesis of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Application In Synthesis of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Recommanded Product: 122567-97-9On October 15, 2021 ,《Multistep Continuous Flow Synthesis of Stavudine》 was published in Journal of Organic Chemistry. The article was written by Sagandira, Cloudius R.; Akwi, Faith M.; Sagandira, Mellisa B.; Watts, Paul. The article contains the following contents:

Herein, we demonstrate an elegant multistep continuous flow synthesis for stavudine (d4T), a potent nucleoside chemotherapeutic agent for human immunodeficiency virus, acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions. This was accomplished via six chem. transformations in five sequential continuous flow reactors from an affordable starting material, 5-methyluridine. In the first instance, single step continuous flow synthesis was demonstrated with an average of 97% yield, 21.4 g/h throughput per step, and a total of 15.5 min residence time. Finally, multistep continuous flow synthesis of d4T in 87% total yield with a total residence time of 19.9 min and 117 mg/h throughput without intermediate purification was demonstrated. In the part of experimental materials, we found many familiar compounds, such as ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Recommanded Product: 122567-97-9)

((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9) 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.Recommanded Product: 122567-97-9

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia