Category: 90213-66-4

In 2018,Tian, Chao; Han, Zifei; Li, Yuanxin; Wang, Meng; Yang, Jiajia; Wang, Xiaowei; Zhang, Zhili; Liu, Junyi published 《Synthesis and biological evaluation of 2,6-disubstituted-9H-purine, 2,4-disubstituted-thieno[3,2-d]pyrimidine and -7H-pyrrolo[2,3-d]pyrimidine analogues as novel CHK1 inhibitors》.European Journal of Medicinal Chemistry published the findings.Recommanded Product: 90213-66-4 The information in the text is summarized as follows:

Arylamino imidazopyrimidines, thienopyrimidines, and pyrrolopyrimidines such as I were prepared as inhibitors of checkpoint kinase 1 (CHK1) for potential use as antitumor agents. I exhibited low anti-proliferative effects towards HT29 and Hek293 cell lines, potentiated the antitumor activity of gemcitabine in HT29 cells, and was selective for CHK1 over a panel of fourteen other kinases. I induced S phase accumulation in gemcitabine-treated HT29 cells. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Recommanded Product: 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. Recommanded Product: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Journal of Medicinal Chemistry included an article by Vazquez, Michael L.; Kaila, Neelu; Strohbach, Joseph W.; Trzupek, John D.; Brown, Matthew F.; Flanagan, Mark E.; Mitton-Fry, Mark J.; Johnson, Timothy A.; TenBrink, Ruth E.; Arnold, Eric P.; Basak, Arindrajit; Heasley, Steven E.; Kwon, Soojin; Langille, Jonathan; Parikh, Mihir D.; Griffin, Sarah H.; Casavant, Jeffrey M.; Duclos, Brian A.; Fenwick, Ashley E.; Harris, Thomas M.; Han, Seungil; Caspers, Nicole; Dowty, Martin E.; Yang, Xin; Banker, Mary Ellen; Hegen, Martin; Symanowicz, Peter T.; Li, Li; Wang, Lu; Lin, Tsung H.; Jussif, Jason; Clark, James D.; Telliez, Jean-Baptiste; Robinson, Ralph P.; Unwalla, Ray. Related Products of 90213-66-4. The article was titled 《Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases》. The information in the text is summarized as follows:

Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. The authors’ efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, the authors discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by x-ray crystallog. anal. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clin. candidate for the treatment of JAK1-mediated autoimmune diseases.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4) was used in this study.

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

Product Details of 90213-66-4In 2021 ,《Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents》 appeared in European Journal of Medicinal Chemistry. The author of the article were Tan, Hanyi; Liu, Yue; Gong, Chaochao; Zhang, Jiawei; Huang, Jian; Zhang, Qian. The article conveys some information:

Focal adhesion kinase (FAK) is a ubiquitous intracellular non-receptor tyrosine kinase, which is involved in multiple cellular functions, including cell adhesion, migration, invasion, survival, and angiogenesis. In this study, a series of 7H-pyrrolo[2,3-d]pyrimidines were designed and synthesized according to the E-pharmacophores generated by docking a library of 667 fragments into the ATP pocket of the co-crystal complex of FAK and PF-562271 (PDB ID: 3BZ3). The 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine derivatives demonstrated excellent activity against FAK and the cell lines SMMC7721 and YY8103. 2-((2-((3-(Acetamidomethyl)phenyl)amino)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-methylbenzamide (I) was selected for further bioactivity evaluations in vivo, including preliminary pharmacokinetic profiling in rats and toxicity assays in mice, and tumor growth inhibition studies in a xenograft tumor model. The results showed that I did not affect the body weight gain of the animals up to a dose of 200 mg/kg, and significantly inhibited tumor growth with a tumor growth inhibition rate of 78.6% compared with the neg. control group. Furthermore, phosphoantibody array analyses of a sample of the tumor suggested that I inhibited the malignant proliferation of hepatocellular carcinoma (HCC) cells through decreasing the phosphorylation in the FAK cascade. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Product Details of 90213-66-4)

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. Product Details of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2014,O’Brien, Nathan J.; Brzozowski, Martin; Buskes, Melissa J.; Deady, Leslie W.; Abbott, Belinda M. published 《Synthesis and biological evaluation of 2-anilino-4-substituted-7H-pyrrolopyrimidines as PDK1 inhibitors》.Bioorganic & Medicinal Chemistry published the findings.Category: pyrimidines The information in the text is summarized as follows:

3-Phosphoinositide-dependent kinase 1 (PDK1), a biol. target that has attracted a large amount of attention recently, is responsible for the pos. regulation of the PI3K/Akt pathway that is often activated in a large number of human cancers. A series of second-generation 2-anilino-4-substituted-7H-pyrrolopyrimidines were synthesized by installation of various functions at the 4-position of the 7H-pyrrolopyrimidine scaffold. All compounds were screened against the isolated PDK1 enzyme and dose response anal. was obtained on the best compounds of the series.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Category: pyrimidines) was used in this study.

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. Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Ding, Xiao; Stasi, Luigi Piero; Ho, Ming-Hsun; Zhao, Baowei; Wang, Hailong; Long, Kai; Xu, Qiongfeng; Sang, Yingxia; Sun, Changhui; Hu, Huan; Yu, Haihua; Wan, Zehong; Wang, Lizhen; Edge, Colin; Liu, Qian; Li, Yi; Dong, Kelly; Guan, Xiaoming; Tattersall, F. David; Reith, Alastair D.; Ren, Feng published 《Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors》.Bioorganic & Medicinal Chemistry Letters published the findings.HPLC of Formula: 90213-66-4 The information in the text is summarized as follows:

Inhibition of LRRK2 kinase activity with small mols. has emerged as a potential novel therapeutic treatment for Parkinson’s disease. Herein the authors disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors identified through a kinase-focused set screening. Optimization of the physicochem. properties and kinase selectivity led to the discovery of compound 7 ((4-((4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone), which exhibited potent in vitro inhibition of LRRK2 kinase activity, good physicochem. properties and kinase selectivity across the kinome. Moreover, compound 7 was able to penetrate into the CNS, and in vivo pharmacol. studies revealed significant inhibition of Ser 935 phosphorylation in the brain of both rats (30 and 100 mg/kg) and mice (45 mg/kg) following oral administration. After reading the article, we found that the author used 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

The author of 《Structure-Based Design of Selective, Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors》 were Rowlands, Rachel A.; Cato, M. Claire; Waldschmidt, Helen V.; Bouley, Renee A.; Chen, Qiuyan; Avramova, Larisa; Larsen, Scott D.; Tesmer, John J. G.; White, Andrew D.. And the article was published in ACS Medicinal Chemistry Letters in 2019. Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

The ability of G protein-coupled receptor (GPCR) kinases (GRKs) to regulate desensitization of GPCRs has made GRK2 and GRK5 attractive targets for treating heart failure and other diseases such as cancer. Although advances have been made toward developing inhibitors that are selective for GRK2, there have been far fewer reports of GRK5 selective compounds Herein, we describe the development of GRK5 subfamily selective inhibitors, 5 and 16d that covalently interact with a nonconserved cysteine (Cys474) unique to this subfamily. Compounds 5 and 16d feature a highly amenable pyrrolopyrimidine scaffold that affords high nanomolar to low micromolar activity that can be easily modified with Michael acceptors with various reactivities and geometries. Our work thereby establishes a new pathway toward further development of subfamily selective GRK inhibitors and establishes Cys474 as a new and useful covalent handle in GRK5 drug discovery. 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 derivatives also play an important role in drug development, either in concert with other compounds or on their own. Application In Synthesis 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 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

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

Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2020 ,《Purine/purine isoster based scaffolds as new derivatives of benzamide class of HDAC inhibitors》 appeared in European Journal of Medicinal Chemistry. The author of the article were Nepali, Kunal; Chang, Ting-Yu; Lai, Mei-Jung; Hsu, Kai-Cheng; Yen, Yun; Lin, Tony Eight; Lee, Sung-Bau; Liou, Jing-Ping. The article conveys some information:

This study reports the design, synthesis and evaluation of a series of histone deacetylase (HDAC) inhibitors I (X = Cl, methylazanyl, (3-chloro-4-fluorophenyl)azanyl, etc.; Y = Cl, NH2, (2,4,6-trichloro-3,5-dimethoxyphenyl)azanyl; Z = N, CH; R = H, F) containing purine/purine isoster as a capping group and an N-(2-aminophenyl)-benzamide unit. In vitro cytotoxicity studies reveal that benzamide I (X = (3-chloro-4-fluorophenyl)azanyl; Y = NH2; Z = N; R = H) (A) suppressed the growth of triple-neg. breast cancer cells MDA-MB-231 (IC50 = 1.48μM), MDA-MB-468 (IC50 = 0.65μM), and liver cancer cells HepG2 (IC50 = 2.44μM), better than MS-275 and Chidamide. Compared to the well-known HDAC inhibitor SAHA, (A) showed a higher toxicity (IC50 = 0.33μM) in three leukemic cell lines, K-562, KG-1 and THP-1. Moreover, (A) was found to be equally virulent in the HDAC-sensitive and -resistant gastric cell lines, YCC11 and YCC3/7, resp., indicating the potential of (A) to overcome HDACi resistance. Furthermore, substantial inhibitory effects more pronounced than MS-275 and Chidamide were displayed by (A) towards HDAC1, 2 and 3 isoforms with IC50 values of 0.108, 0.585 and 0.563μM resp. Compound (A) also exhibited a potent antitumor efficacy in human MDA-MB-231 breast cancer xenograft mouse model, providing a potential lead for the development of anticancer agents. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Safety 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. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia