Category: 90213-66-4

《Structure-Guided Optimization Provides a Series of TTK Protein Inhibitors with Potent Antitumor Activity》 was written by Elsner, Jan; Cashion, Dan; Robinson, Dale; Bahmanyar, Sogole; Tehrani, Lida; Fultz, Kimberly E.; Narla, Rama Krishna; Peng, Xiaohui; Tran, Tam; Apuy, Julius; LeBrun, Laurie; Leftheris, Katerina; Boylan, John F.; Zhu, Dan; Riggs, Jennifer R.. Product Details of 90213-66-4This research focused onTTK kinase inhibitor preparation cancer. The article conveys some information:

TTK is an essential spindle assembly checkpoint enzyme in many organisms. It plays a central role in tumor cell proliferation and is aberrantly overexpressed in a wide range of tumor types. We recently reported on a series of potent and selective TTK inhibitors with strong antiproliferative activity in triple neg. breast cancer (TNBC) cell lines (8: TTK IC50 = 3.0 nM; CAL-51 IC50 = 84.0 nM). Inspired by previously described potent tricyclic TTK inhibitor 6 (TTK IC50 = 0.9 nM), we embarked on a structure-enabled design and optimization campaign to identify an improved series with excellent potency, TTK selectivity, solubility, CYP inhibition profile, and in vivo efficacy in a TNBC xenograft model. These efforts culminated in the discovery of 25 (TTK IC50 = 3.0 nM; CAL-51 IC50 = 16.0 nM), which showed significant single-agent efficacy when dosed iv in a TNBC xenograft model without body weight loss. In the experiment, the researchers used many compounds, for example, 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 2018,Chen, Dizhong; Soh, Chang Kai; Goh, Wei Huang; Wang, Haishan published 《Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma》.Journal of Medicinal Chemistry published the findings.Electric Literature of C6H3Cl2N3 The information in the text is summarized as follows:

Class I histone deacetylases (HDACs) are highly expressed and/or upregulated in hepatocellular carcinoma (HCC) and are associated with aggressiveness, spread, and increased mortality of HCC. Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. A series of purine or 5H-pyrrolo[3,2-d]pyrimidine based hydroxamates were designed and developed as multitarget drugs to modulate both HDACs and the PI3K/Akt/mTOR pathway. Among 39 cell lines screened, the mols. (e.g., I, II, and III) were the most selective against leukemia, lymphoma, and HCC cells; they also demonstrated target modulation in cancer cell lines and in mice bearing MV4-11 and HepG2 tumors. Compound II in particular showed significant single agent oral efficacy in hypervascular liver cancer models (e.g., HepG2, HuH-7, and Hep3B) and was well-tolerated. These encouraging results, along with its favorable target profile and tissue distribution, warrant further development of II. The experimental process involved the reaction of 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

In 2016,Liang, Xuewu; Zang, Jie; Zhu, Mengyuan; Gao, Qianwen; Wang, Binghe; Xu, Wenfang; Zhang, Yingjie published 《Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1H)-pyrazole Derivatives as JAKs Inhibitors》.ACS Medicinal Chemistry Letters published the findings.Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The information in the text is summarized as follows:

Abnormalities in the JAK/STAT signaling pathway lead to many diseases such as immunodeficiency, inflammation, and cancer. Herein, we designed and synthesized a series of 4-amino-(1H)-pyrazole derivatives as potent JAKs inhibitors for cancer treatment. Results from in vitro protein kinase inhibition experiments indicated that some compounds are potent JAKs inhibitors. For example, the IC50 values of compound I against JAK1, JAK2, and JAK3 were 3.4, 2.2, and 3.5 nM, resp. In cell culture experiments, compound I showed potent antiproliferative activity against various cell lines (PC-3, HEL, K562, MCF-7, and MOLT4) at low micromolar levels, while compound II showed selective cytotoxicity at submicromolar levels against HEL (IC50: 0.35 μM) and K562 (IC50: 0.37 μM) cell lines. It is worth noting that both I and II showed more potent antiproliferative activities than the approved JAKs inhibitor Ruxolitinib. In addition to this study using 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine, there are many other studies that have used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Quality Control of 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. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Quality Control of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2016,Sabat, Nazarii; Postova Slavetinska, Lenka; Klepetarova, Blanka; Hocek, Michal published 《C-H Phosphonation of Pyrrolopyrimidines: Synthesis of Substituted 7- and 9-Deazapurine-8-phosphonate Derivatives》.Journal of Organic Chemistry published the findings.Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The information in the text is summarized as follows:

The Mn(OAc)3-promoted C-H phosphonation of 7-deazapurines (pyrrolo[2,3-d]pyrimidines) and 9-deazapurines (pyrrolo[3,2-d]pyrimidines) with diethylphosphite was developed. The reactions occur regioselectively at position 8 both in 7 and 9-deazapurines, leading to new deazapurine-8-phosphonate derivatives, which can be further modified and transformed to 6-(het)aryl-deazapurine derivatives or deprotected to free phosphonic acids. In addition to this study using 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine, there are many other studies that have used 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. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Name: 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

SDS of cas: 90213-66-4In 2021 ,《Structure-Based Design and Discovery of Pyridyl-Bearing Fused Bicyclic HIV-1 Inhibitors: Synthesis, Biological Characterization, and Molecular Modeling Studies》 was published in Journal of Medicinal Chemistry. The article was written by Huang, Boshi; Ginex, Tiziana; Luque, F. Javier; Jiang, Xiangyi; Gao, Ping; Zhang, Jian; Kang, Dongwei; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. The article contains the following contents:

Tetrahydroquinazolines I [R1 = Me, CN, CHO, CH2=CH2CN; R2 = CN, CH2CN, OCF3, SO2CH3; X = Y = CH, N]/pyrrolopyrimidines II [R3 = CN, CH2=CH2CN, CH2=CH2C(O)NH2; X1 = CH, N; Y1 = CH]/pyrrolotriazines III [R4 = CH2OH, CH2O(CH2)2Si(CH3)3, 2-morpholino-2-oxo-ethyl; X2 = Y2 = CH, N] analogs designed to target the dual-tolerant regions of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-binding pocket were synthesized and evaluated for their anti-HIV activities. Several compounds, such as I [R1 = CN, CH2=CH2CN; R2 = CN; X = Y = CH], compound II [R3 = CN; X1 = N; Y1 = CH] and compounds III [R4 = CH2OH, 2-morpholino-2-oxo-ethyl; X2 = CH, N; Y2 = CH] were found to be potent inhibitors against the wild-type (WT) HIV-1 strain or multiple NNRTI-resistant strains at low nanomolar levels. Detailed structure-activity relationships were obtained by utilizing the variation of moieties within the corresponding pharmacophores. In vitro metabolic stability profiles and some drug-like properties of selected compounds were assessed, furnishing the preliminary structure-metabolic stability relationships. Furthermore, mol. modeling studies elucidated the binding modes of compounds I [R1 = CN, CH2=CH2CN; R2 = CN; X = CH, N; Y = CH], compound II [R3 = CN; X1 = N; Y1 = CH] and compound III [R4 = CH2OH; X2 = CH, N; Y2 = CH] in the binding pocket of WT, E138K, K103N, or Y181C HIV-1 RTs. These promising compounds could be used as lead compounds and warrant further structural optimization to yield more active HIV-1 inhibitors.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4SDS of cas: 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. SDS of cas: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 90213-66-4In 2010 ,《Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors》 appeared in Journal of Medicinal Chemistry. The author of the article were Chen, Zecheng; Venkatesan, Aranapakam M.; Dehnhardt, Christoph M.; Ayral-Kaloustian, Semiramis; Brooijmans, Natasja; Mallon, Robert; Feldberg, Larry; Hollander, Irwin; Lucas, Judy; Yu, Ker; Kong, Fangming; Mansour, Tarek S.. The article conveys some information:

A series of (4-morpholino)pyrrolopyrimidine derivatives were synthesized and evaluated as inhibitors of PI3Kα and mTOR, leading to the discovery of PI3Kα selective inhibitors (e.g., I) and dual PI3Kα/mTOR kinase inhibitors (e.g., II). PI3Kα/mTOR dual inhibitors demonstrated inhibition of tumor cell growth in vitro and in vivo and caused suppression of the pathway specific biomarkers [e.g., the phosphorylation of Akt at Thr308 (T308) and Ser473 (S473)] in the human breast cancer cell line MDA361. In addition, compound II demonstrated good in vivo efficacy in the MDA361 human breast tumor xenograft model. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4SDS of cas: 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. SDS of cas: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 1995,Serafinowski, Pawel; Dorland, Erwin; Balzarini, Jan; De Clercq, Erik published 《The synthesis and antiviral activity of some new S-adenosyl-L-homocysteine derivatives and their nucleoside precursors》.Nucleosides & Nucleotides published the findings.Application of 90213-66-4 The information in the text is summarized as follows:

S-adenosyl-L-homocysteine derivatives I (R = Cl, Me) were prepared and tested for their antiviral activity. In the experimental materials used by the author, we found 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,Bioorganic & Medicinal Chemistry included an article by Fuerst, Rita; Yong Choi, Jun; Knapinska, Anna M.; Smith, Lyndsay; Cameron, Michael D.; Ruiz, Claudia; Fields, Gregg B.; Roush, William R.. Product Details of 90213-66-4. The article was titled 《Development of matrix metalloproteinase-13 inhibitors – A structure-activity/structure-property relationship study》. The information in the text is summarized as follows:

A structure-activity/structure-property relationship study based on the physicochem. as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhibitor 2, compound 31 was identified which exhibited microsomal half-life higher than 20 min, kinetic solubility higher than 20 μM, and a permeability coefficient greater than 20 × 10-6 cm/s. Compound 31 also showed excellent in vivo PK properties after IV dosing (Cmax = 56.8 μM, T1/2 (plasma) = 3.0 h, Cl = 0.23 mL/min/kg) and thus is a suitable candidate for in vivo efficacy studies in an OA animal model. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Product Details of 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. Product Details of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Davis, Ryan R.; Li, Baoli; Yun, Sang Y.; Chan, Alice; Nareddy, Pradeep; Gunawan, Steven; Ayaz, Muhammad; Lawrence, Harshani R.; Reuther, Gary W.; Lawrence, Nicholas J.; Schonbrunn, Ernst published an article in 2021. The article was titled 《Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof》, and you may find the article in Journal of Medicinal Chemistry.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:

The discovery that aberrant activity of Janus kinase 2 (JAK2) is a driver of myeloproliferative neoplasms (MPNs) has led to significant efforts to develop small mol. inhibitors for this patient population. Ruxolitinib and fedratinib have been approved for use in MPN patients, while baricitinib, an achiral analog of ruxolitinib, has been approved for rheumatoid arthritis. However, structural information on the interaction of these therapeutics with JAK2 remains unknown. Here, we describe a new methodol. for the large-scale production of JAK2 from mammalian cells, which enabled us to determine the first crystal structures of JAK2 bound to these drugs and derivatives thereof. Along with biochem. and cellular data, the results provide a comprehensive view of the shape complementarity required for chiral and achiral inhibitors to achieve highest activity, which may facilitate the development of more effective JAK2 inhibitors as therapeutics. The results came from multiple reactions, including the reaction of 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

Electric Literature of C6H3Cl2N3In 2021 ,《Discovery of 6-[(3S,4S)-4-Amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methyl-3,4-dihydropyrimidin-4-one (IACS-15414), a Potent and Orally Bioavailable SHP2 Inhibitor》 appeared in Journal of Medicinal Chemistry. The author of the article were Czako, Barbara; Sun, Yuting; McAfoos, Timothy; Cross, Jason B.; Leonard, Paul G.; Burke, Jason P.; Carroll, Christopher L.; Feng, Ningping; Harris, Angela L.; Jiang, Yongying; Kang, Zhijun; Kovacs, Jeffrey J.; Mandal, Pijus; Meyers, Brooke A.; Mseeh, Faika; Parker, Connor A.; Yu, Simon S.; Williams, Christopher C.; Wu, Qi; Di Francesco, Maria Emilia; Draetta, Giulio; Heffernan, Timothy; Marszalek, Joseph. R.; Kohl, Nancy E.; Jones, Philip. The article conveys some information:

Src homol. 2 (SH2) domain-containing phosphatase 2 (SHP2) plays a role in receptor tyrosine kinase (RTK), neurofibromin-1 (NF-1), and Kirsten rat sarcoma virus (KRAS) mutant-driven cancers, as well as in RTK-mediated resistance, making the identification of small-mol. therapeutics that interfere with its function of high interest. Our quest to identify potent, orally bioavailable, and safe SHP2 inhibitors led to the discovery of a promising series of pyrazolopyrimidinones that displayed excellent potency but had a suboptimal in vivo pharmacokinetic (PK) profile. Hypothesis-driven scaffold optimization led us to a series of pyrazolopyrazines with excellent PK properties across species but a narrow human Ether-á-go-go-Related Gene (hERG) window. Subsequent optimization of properties led to the discovery of the pyrimidinone series, in which multiple members possessed excellent potency, optimal in vivo PK across species, and no off-target activities including no hERG liability up to 100μM. Importantly, compound 30 (IACS-15414) potently suppressed the mitogen-activated protein kinase (MAPK) pathway signaling and tumor growth in RTK-activated and KRASmut xenograft models in vivo. The results came from multiple reactions, including the reaction of 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 nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Electric Literature of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia