Category: 90213-66-4

The author of 《Process Development and Scale Up of a Selective JAK3 Covalent Inhibitor PF-06651600》 were Tao, Yong; McWilliams, J. Christopher; Wiglesworth, Kristin E.; Girard, Kevin P.; Makowski, Teresa M.; Sach, Neal W.; Mustakis, Jason G.; Mehta, Ruchi; Trujillo, John I.; Chen, Xiaofeng; Li, Tangqing; Shi, Feng; Xie, Chengfu; Zhang, Qing. And the article was published in Organic Process Research & Development in 2019. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

A scalable process for PF-06651600 was developed through successful enabling of the first generation synthesis. The synthesis highlights include the following: (1) replacement of costly PtO2 with a less expensive 5% Rh/C catalyst for a pyridine hydrogenation, (2) identification of a diasteromeric salt crystallization to isolate the enantiomerically pure cis-isomer directly from a racemic mixture of cis/trans isomers, (3) a high yielding amidation via Schotten-Baumann conditions, and (4) critical development of a reproducible crystallization procedure for a stable crystalline salt 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one p-Toluenesulfonate, which is suitable for long-term storage and tablet formulation. All chromatog. purifications, including two chiral SFC chromatog. separations, were eliminated. Combined with other improvements in each step of the synthesis, the overall yield was increased from 5% to 14%. Several multikilogram batches of the API were delivered to support clin. studies. 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

Makova, Barbara; Mik, Vaclav; Liskova, Barbora; Gonzalez, Gabriel; Vitek, Dominik; Medvedikova, Martina; Monfort, Beata; Rucilova, Veronika; Kadlecova, Alena; Khirsariya, Prashant; Gandara Barreiro, Zoila; Havlicek, Libor; Zatloukal, Marek; Soural, Miroslav; Paruch, Kamil; D’Autreaux, Benoit; Hajduch, Marian; Strnad, Miroslav; Voller, Jiri published an article in 2021. The article was titled 《Cytoprotective activities of kinetin purine isosteres》, and you may find the article in Bioorganic & Medicinal Chemistry.Electric Literature of C6H3Cl2N3 The information in the text is summarized as follows:

Kinetin (N6-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here, the authors report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biol. evaluation of their activity in several in vitro models related to neurodegenerative diseases. The findings indicate that kinetin isosteres protect Friedreichs ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, this data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach the central nervous system. Overall, the data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biol. activities of kinetin and discovering novel therapeutic opportunities. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Electric Literature of C6H3Cl2N3)

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. Electric Literature of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2012 ,《Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization》 appeared in European Journal of Medicinal Chemistry. The author of the article were Xie, Hui; Zeng, Lili; Zeng, Shaogao; Lu, Xin; Zhang, Guicheng; Zhao, Xin; Cheng, Na; Tu, Zhengchao; Li, Zhiyuan; Xu, Hongjiang; Yang, Ling; Zhang, Xiquan; Huang, Min; Zhao, Junling; Hu, Wenhui. The article conveys some information:

We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biol. activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine) 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. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 90213-66-4In 2015 ,《Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor》 appeared in ACS Medicinal Chemistry Letters. The author of the article were Hatcher, John M.; Zhang, Jinwei; Choi, Hwan Geun; Ito, Genta; Alessi, Dario R.; Gray, Nathanael S.. The article conveys some information:

Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson’s disease (PD) patients and may represent an attractive therapeutic target. Here the authors report JH-II-127 I, as a potent and selective inhibitor of both wild-type and G2019S mutant LRRK2. Compound I substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 μM in a variety of cell types and is capable of inhibiting Ser935 phosphorylation in mouse brain following oral delivery of doses as low as 30 mg/kg. 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

SDS of cas: 90213-66-4In 2022 ,《Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer》 appeared in European Journal of Medicinal Chemistry. The author of the article were Wei, Wei; Feng, Zhanzhan; Liu, Zhihao; Li, Xinyue; He, Hualong; Ran, Kai; Shi, Yaojie; Zhu, Yongxia; Ye, Tinghong; Gao, Chao; Wang, Ningyu; Yu, Luoting. The article conveys some information:

Focal adhesion kinase (FAK) promotes tumor progression by intracellular signal transduction and regulation of gene expression and protein turnover, which is a compelling therapeutic target for various cancer types, including ovarian cancer. However, the clin. responses of FAK inhibitors remain unsatisfactory. Here, we describe the discovery of FAK inhibitors using a scaffold hopping strategy. Structure-activity relationship (SAR) exploration identified 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide as a potent FAK inhibitor, which exhibited inhibitory activities against FAK signaling in vitro. Treatment with 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide not only decreased migration and invasion of PA-1 cells, but also reduced expression of MMP-2 and MMP-9. Moreover, 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide inhibited tumor growth and metastasis, and no obvious adverse effects were observed during the in vivo study. These results revealed the potential of FAK inhibitor 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(piperidin-4-yl)benza-mide for treatment of ovarian cancer. In the experiment, the researchers 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

In 2015,Samanta, Ramesh C.; Yamamoto, Hisashi published 《Selective Halogenation Using an Aniline Catalyst》.Chemistry – A European Journal published the findings.Electric Literature of C6H3Cl2N3 The information in the text is summarized as follows:

Electrophilic halogenation was used to produce a wide variety of halogenated compounds The arylamines were found to generate an N-halo arylamine intermediate, which acts as a highly reactive but selective catalytic electrophilic halogen source. A wide variety of heteroaromatic and aromatic compounds were halogenated using com. available N-halosuccinimides, for example, NCS, NBS, and NIS, with good to excellent yields and with very high selectivity. In the case of unactivated double bonds, allylic chlorides were obtained under chlorination conditions, whereas bromocyclization occurred for polyolefin. The reactivity of the catalyst could be tuned by varying the electronic properties of the arene moiety of catalyst. In the experiment, the researchers used many compounds, for example, 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. 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. Electric Literature of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of AB680: A Potent and Selective Inhibitor of CD73》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Lawson, Kenneth V.; Kalisiak, Jaroslaw; Lindsey, Erick A.; Newcomb, Eric T.; Leleti, Manmohan Reddy; Debien, Laurent; Rosen, Brandon R.; Miles, Dillon H.; Sharif, Ehesan U.; Jeffrey, Jenna L.; Tan, Joanne B. L.; Chen, Ada; Zhao, Sharon; Xu, Guifen; Fu, Lijuan; Jin, Lixia; Park, Tim W.; Berry, Wade; Moschutz, Susanne; Scaletti, Emma; Strater, Norbert; Walker, Nigel P.; Young, Stephen W.; Walters, Matthew J.; Schindler, Uli; Powers, Jay P.. COA of Formula: C6H3Cl2N3 The article mentions the following:

Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. Extensive interrogation of structure-activity relationships (SARs), structure-based drug design, and optimization of pharmacokinetic properties culminated in the discovery of AB680, a highly potent (Ki = 5 pM), reversible, and selective inhibitor of CD73. AB680 is further characterized by very low clearance and long half-lives across preclin. species, resulting in a PK profile suitable for long-acting parenteral administration. AB680 is currently being evaluated in phase 1 clin. trials. Initial data show AB680 is well tolerated and exhibits a pharmacokinetic profile suitable for biweekly (Q2W) iv-administration in human. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4COA of Formula: 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. COA of Formula: C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design and optimization leading to an orally active TTK protein kinase inhibitor with robust single agent efficacy》 was written by Riggs, Jennifer R.; Elsner, Jan; Cashion, Dan; Robinson, Dale; Tehrani, Lida; Nagy, Mark; Fultz, Kimberly E.; Krishna Narla, Rama; Peng, Xiaohui; Tran, Tam; Kulkarni, Ashutosh; Bahmanyar, Sogole; Condroski, Kevin; Pagarigan, Barbra; Fenalti, Gustavo; LeBrun, Laurie; Leftheris, Katerina; Zhu, Dan; Boylan, John F.. Application of 90213-66-4This research focused ontriple neg breast cancer antitumor TTK protein kinase pharmacokinetics. The article conveys some information:

Triple neg. breast cancer (TNBC) is an aggressive disease with high relapse rates and few treatment options. Outlined in previous publications, we identified a series of potent, dual TTK/CLK2 inhibitors with strong efficacy in TNBC xenograft models. Pharmacokinetic properties and kinome selectivity were optimized, resulting in the identification of a new series of potent, selective, and orally bioavailable TTK inhibitors. We describe here the structure-activity relationship of the 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine series, leading to significant single agent efficacy in a TNBC xenograft model without body weight loss. The design effort evolving an iv-dosed TTK/CLK2 inhibitor to an orally bioavailable TTK inhibitor is described. The results came from multiple reactions, including the reaction of 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 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 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

COA of Formula: C6H3Cl2N3In 2017 ,《Novel pyrrolopyrimidines as Mps1/TTK kinase inhibitors for breast cancer》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Sugimoto, Yasuro; Sawant, Dwitiya B.; Fisk, Harold A.; Mao, Liguang; Li, Chenglong; Chettiar, Somsundaram; Li, Pui-Kai; Darby, Michael V.; Brueggemeier, Robert W.. The article conveys some information:

New targeted therapy approaches for certain subtypes of breast cancer, such as triple-neg. breast cancers and other aggressive phenotypes, are desired. High levels of the mitotic checkpoint kinase Mps1/TTK have correlated with high histol. grade in breast cancer, suggesting a potential new therapeutic target for aggressive breast cancers (BC). Novel small mols. targeting Mps1 were designed by computer assisted docking analyses, and several candidate compounds were synthesized. These compounds were evaluated in anti-proliferative assays of a panel of 15 breast cancer cell lines and further examined for their ability to inhibit a variety of Mps1-dependent biol. functions. The results indicate that the lead compounds have strong anti-proliferative potential through Mps1/TTK inhibition in both basal and luminal BC cell lines, exhibiting IC50 values ranging from 0.05 to 1.0 μM. In addition, the lead compounds 1 and 13 inhibit Mps1 kinase enzymic activity with IC50 values from 0.356 μM to 0.809 μM, and inhibited Mps1-associated cellular functions such as centrosome duplication and the spindle checkpoint in triple neg. breast cancer cells. The most promising analog, compound 13, significantly decreased tumor growth in nude mice containing Cal-51 triple neg. breast cancer cell xenografts. Using drug discovery technologies, computational modeling, medicinal chem., cell culture and in vivo assays, novel small mol. Mps1/TTK inhibitors have been identified as potential targeted therapies for breast cancers. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4COA of Formula: 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. COA of Formula: C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2009 ,《Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma》 appeared in Journal of Medicinal Chemistry. The author of the article were Harrison, Bryce A.; Whitlock, N. Andrew; Voronkov, Michael V.; Almstead, Zheng Y.; Gu, Kun-Jian; Mabon, Ross; Gardyan, Michael; Hamman, Brian D.; Allen, Jason; Gopinathan, Suma; McKnight, Beth; Crist, Mike; Zhang, Yulian; Liu, Ying; Courtney, Lawrence F.; Key, Billie; Zhou, Julia; Patel, Nita; Yates, Phil W.; Liu, Qingyun; Wilson, Alan G. E.; Kimball, S. David; Crosson, Craig E.; Rice, Dennis S.; Rawlins, David B.. The article conveys some information:

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma. In the experiment, the researchers used many compounds, for example, 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