Category: 90213-66-4

In 2016,Cheng, Hengmiao; Nair, Sajiv K.; Murray, Brion W.; Almaden, Chau; Bailey, Simon; Baxi, Sangita; Behenna, Doug; Cho-Schultz, Sujin; Dalvie, Deepak; Dinh, Dac M.; Edwards, Martin P.; Feng, Jun Li; Ferre, Rose Ann; Gajiwala, Ketan S.; Hemkens, Michelle D.; Jackson-Fisher, Amy; Jalaie, Mehran; Johnson, Ted O.; Kania, Robert S.; Kephart, Susan; Lafontaine, Jennifer; Lunney, Beth; Liu, Kevin K.-C.; Liu, Zhengyu; Matthews, Jean; Nagata, Asako; Niessen, Sherry; Ornelas, Martha A.; Orr, Suvi T. M.; Pairish, Mason; Planken, Simon; Ren, Shijian; Richter, Daniel; Ryan, Kevin; Sach, Neal; Shen, Hong; Smeal, Tod; Solowiej, Jim; Sutton, Scott; Tran, Khanh; Tseng, Elaine; Vernier, William; Walls, Marlena; Wang, Shuiwang; Weinrich, Scott L.; Xin, Shuibo; Xu, Haiwei; Yin, Min-Jean; Zientek, Michael; Zhou, Ru; Kath, John C. published 《Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants》.Journal of Medicinal Chemistry published the findings.HPLC of Formula: 90213-66-4 The information in the text is summarized as follows:

First generation EGFR TKIs (gefitinib, erlotinib) provide significant clin. benefit for NSCLC cancer patients with oncogenic EGFR mutations. Ultimately, these patients’ disease progresses, often driven by a second-site mutation in the EGFR kinase domain (T790M). Another liability of the first generation drugs is severe adverse events driven by inhibition of WT EGFR. As such, our goal was to develop a highly potent irreversible inhibitor with the largest selectivity ratio between the drug-resistant double mutants (L858R/T790M, Del/T790M) and WT EGFR. A unique approach to develop covalent inhibitors, optimization of reversible binding affinity, served as a cornerstone of this effort. PF-06459988 was discovered as a novel, third generation irreversible inhibitor, which demonstrates (i) high potency and specificity to the T790M-containing double mutant EGFRs, (ii) minimal intrinsic chem. reactivity of the electrophilic warhead, (iii) greatly reduced proteome reactivity relative to earlier irreversible EGFR inhibitors, and (iv) minimal activity against WT EGFR. 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

SDS of cas: 90213-66-4In 2019 ,《Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H3 receptor》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Frank, Annika; Meza-Arriagada, Francisco; Salas, Cristian O.; Espinosa-Bustos, Christian; Stark, Holger. The article conveys some information:

Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H3 receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, Ki value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4′-bipiperidin]-1′-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (Ki values of 7 nM and 6 nM, resp.) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H3 receptor ligands and yielded novel lead structures within the natural compound library against this target. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4SDS of cas: 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. SDS of cas: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Category: pyrimidinesIn 2017 ,《Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase》 appeared in Journal of Medicinal Chemistry. The author of the article were Brough, Paul A.; Baker, Lisa; Bedford, Simon; Brown, Kirsten; Chavda, Seema; Chell, Victoria; D’Alessandro, Jalanie; Davies, Nicholas G. M.; Davis, Ben; Le Strat, Loic; Macias, Alba T.; Maddox, Daniel; Mahon, Patrick C.; Massey, Andrew J.; Matassova, Natalia; McKenna, Sean; Moore, Jonathan D.; Murray, James B.; Northfield, Christopher J.; Parry, Charles; Parsons, Rachel; Roughley, Stephen D.; Shaw, Terry; Simmonite, Heather; Stokes, Stephen; Surgenor, Allan; Stefaniak, Emma; Robertson, Alan; Wang, Yikang; Webb, Paul; Whitehead, Neil; Wood, Mike. The article conveys some information:

Libraries of non-purified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro. In the experimental materials used by the author, we found 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 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 2022,Boffey, Helen K.; Rooney, Timothy P. C.; Willems, Henriette M. G.; Edwards, Simon; Green, Christopher; Howard, Tina; Ogg, Derek; Romero, Tamara; Scott, Duncan E.; Winpenny, David; Duce, James; Skidmore, John; Clarke, Jonathan H.; Andrews, Stephen P. published an article in Journal of Medicinal Chemistry. The title of the article was 《Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode》.HPLC of Formula: 90213-66-4 The author mentioned the following in the article:

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunol. disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochem. properties of the selective PI5P4Kγ inhibitor, NIH-12848 (1). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kβ. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chem. series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4HPLC of Formula: 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. HPLC of Formula: 90213-66-4

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 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

In 1988,Saxena, Naveen K.; Hagenow, Brenda M.; Genzlinger, Gail; Turk, Steven R.; Drach, John C.; Townsend, Leroy B. published 《Synthesis and antiviral activity of certain 4-substituted and 2,4-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidines》.Journal of Medicinal Chemistry published the findings.Product Details of 90213-66-4 The information in the text is summarized as follows:

Alkylation of the Na salt of pyrimidine I (R = MeS, R1 = H) with AcOCH2CH2OCH2Br gave I (R = MeS, R1 = AcOCH2CH2OCH2) which was converted into the title pyrimidines II (R = MeS, R2 = Cl, NH2; R = H, OH, MeSO2, MeO, R2 = NH2). Similarly, I (R = Cl, NHAc, R1 = H) were alkylated and further transformed into II (R = Cl, R2 = Cl, NH2; R = NHAc, R2 = Cl; R = R2 = NH2). In tests of II involving human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), only slight activity and cytotoxicity were observed The most active compounds I(R = Cl, R1 = AcOCH2CH2OCH2) and II (R = R2 = Cl), were slightly more active against HCMV than acyclovir, but both compounds were inactive against HSV-1. The activity against HCMV, however, was not well separated from cytotoxicity leading to the conclusion that these compounds did not merit further study. 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 derivatives also play an important role in drug development, either in concert with other compounds or on their own. Product Details 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 2017,Xie, Hui; Zeng, Shaogao; He, Yuwen; Zhang, Guicheng; Yu, Pengjiu; Zhong, Guifa; Xu, Hongjiang; Yang, Ling; Wang, Shanchun; Zhao, Xin; Hu, Wenhui published 《Rapid generation of a novel DPP-4 inhibitor with long-acting properties: SAR study and PK/PD evaluation》.European Journal of Medicinal Chemistry published the findings.Related Products of 90213-66-4 The information in the text is summarized as follows:

Drug compliance is critical for patients with chronic diseases such as diabetes. In our continuous effort to find better glucose-lowering agents, an exploration for long-acting DPP-4 inhibitors had been launched. Based on our previously reported compounds bearing a pyrrolopyrimidine scaffold, the lead compound 4a (IC50 = 2.3 nM, t1/2(rat) = 5.46 h) with pharmacokinetic superiority was rapidly determined Further SAR study indicated that the pyrrole ring was generally tolerable for variation, in which a β-substitution gave a better DPP-4 affinity. In depth evaluation of the pyrrole ring β position identified a highly potent compound 12a (IC50 = 0.76 nM, t1/2(rat) = 7.89 h). In vivo pharmacodynamics tests demonstrated similar or even slightly better sustained DPP-4 inhibition for compounds 4a and 12a compared with the first marketed once-weekly drug trelagliptin in this category, indicating that improvements to DPP-4 inhibitory activity or pharmacokinetic profile might be feasible ways to rapidly generate long-acting DPP-4 inhibitors. The experimental process involved the reaction of 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. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Related Products 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 2017,Thorarensen, Atli; Dowty, Martin E.; Banker, Mary Ellen; Juba, Brian; Jussif, Jason; Lin, Tsung; Vincent, Fabien; Czerwinski, Robert M.; Casimiro-Garcia, Agustin; Unwalla, Ray; Trujillo, John I.; Liang, Sidney; Balbo, Paul; Che, Ye; Gilbert, Adam M.; Brown, Matthew F.; Hayward, Matthew; Montgomery, Justin; Leung, Louis; Yang, Xin; Soucy, Sarah; Hegen, Martin; Coe, Jotham; Langille, Jonathan; Vajdos, Felix; Chrencik, Jill; Telliez, Jean-Baptiste published 《Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans》.Journal of Medicinal Chemistry published the findings.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:

Significant work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds entering clin. development and two FDA approved NMEs. However, despite significant effort during the past two decades, identification of highly selective JAK3 inhibitors has eluded the scientific community. A significant effort within the research organization has resulted in the identification of the first orally active JAK3 specific inhibitor, which achieves JAK isoform specificity through covalent interaction with a unique JAK3 residue Cys-909. The relatively rapid resynthesis rate of the JAK3 enzyme presented a unique challenge in the design of covalent inhibitors with appropriate pharmacodynamics properties coupled with limited unwanted off-target reactivity. This effort resulted in the identification of PF-06651600 I, a potent and low clearance compound with demonstrated in vivo efficacy. The favorable efficacy and safety profile of this specific JAK3 inhibitor I led to its evaluation in several human clin. studies. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Synthetic Route of 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. Synthetic Route of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Early Process Development of an Irreversible Epidermal Growth Factor Receptor (EGFR) T790 M Inhibitor》 were Tao, Yong; Keene, Nandell F.; Wiglesworth, Kristin E.; Sitter, Barbara; McWilliams, J. Christopher. And the article was published in Organic Process Research & Development in 2019. Electric Literature of C6H3Cl2N3 The author mentioned the following in the article:

The original synthesis of the irreversible epidermal growth factor receptor (EGFR) T790 M inhibitor 1 (I) was enabled by successful application of ammonium hydroxide to cleanly cleave the N-hydroxymethyl group and by development of high yielding conditions for the subsequent amidation reaction. Furthermore, a protection-free and regioselective new synthetic route was developed that shortened the synthesis from the original 8 steps to 6 steps and improved the overall yield from 5% to 34% on scale. Crystallizations of 1 and intermediates were correspondingly developed to control the quality en route. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Electric Literature of C6H3Cl2N3)

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. Electric Literature of C6H3Cl2N3They 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