Category: pyrimidines

Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas was written by Lito, Piro;Pratilas, Christine A.;Joseph, Eric W.;Tadi, Madhavi;Halilovic, Ensar;Zubrowski, Matthew;Huang, Alan;Wong, Wai Lin;Callahan, Margaret K.;Merghoub, Taha;Wolchok, Jedd D.;de Stanchina, Elisa;Chandarlapaty, Sarat;Poulikakos, Poulikos I.;Fagin, James A.;Rosen, Neal. And the article was included in Cancer Cell in 2012.Safety of 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea The following contents are mentioned in the article:

BRAF^V600E drives tumors by dysregulating ERK signaling. In these tumors, we show that high levels of ERK-dependent neg. feedback potently suppress ligand-dependent mitogenic signaling and Ras function. BRAF^V600E activation is Ras independent and it signals as a RAF-inhibitor-sensitive monomer. RAF inhibitors potently inhibit RAF monomers and ERK signaling, causing relief of ERK-dependent feedback, reactivation of ligand-dependent signal transduction, increased Ras-GTP, and generation of RAF-inhibitor-resistant RAF dimers. This results in a rebound in ERK activity and culminates in a new steady state, wherein ERK signaling is elevated compared to its initial nadir after RAF inhibition. In this state, ERK signaling is RAF inhibitor resistant, and MEK inhibitor sensitive, and combined inhibition results in enhancement of ERK pathway inhibition and antitumor activity. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Safety of 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Safety of 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors was written by Bavetsias, Vassilios;Lanigan, Rachel M.;Ruda, Gian Filippo;Atrash, Butrus;McLaughlin, Mark G.;Tumber, Anthony;Mok, N. Yi;Le Bihan, Yann-Vai;Dempster, Sally;Boxall, Katherine J.;Jeganathan, Fiona;Hatch, Stephanie B.;Savitsky, Pavel;Velupillai, Srikannathasan;Krojer, Tobias;England, Katherine S.;Sejberg, Jimmy;Thai, Ching;Donovan, Adam;Pal, Akos;Scozzafava, Giuseppe;Bennett, James M.;Kawamura, Akane;Johansson, Catrine;Szykowska, Aleksandra;Gileadi, Carina;Burgess-Brown, Nicola A.;von Delft, Frank;Oppermann, Udo;Walters, Zoe;Shipley, Janet;Raynaud, Florence I.;Westaway, Susan M.;Prinjha, Rab K.;Fedorov, Oleg;Burke, Rosemary;Schofield, Christopher J.;Westwood, Isaac M.;Bountra, Chas;Muller, Susanne;van Montfort, Rob L. M.;Brennan, Paul E.;Blagg, Julian. And the article was included in Journal of Medicinal Chemistry in 2016.Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid The following contents are mentioned in the article:

We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-Me lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity vs. the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me₃ and H3K4Me₃ demethylation in a cell-based assay. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid).

3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Osmometric studies on self-association of pyrimidines in aqueous solutions: evidence for involvement of hydrophobic interactions was written by Plesiewicz, Ewa;Stepien, Elzbieta;Bolewska, Krystyna;Wierzchowski, K. L.. And the article was included in Biophysical Chemistry in 1976.HPLC of Formula: 39513-47-8 The following contents are mentioned in the article:

Vapor pressure osmometric studies were performed on stacking self-association of 25 uracil derivatives variously C- and N-substituted with polar and alkyl groups in aqueous solution at various temperatures The respective equilibrium association constants KSt were computed on the assumption of the isodesmic model of self-association Enthalpies of association for most of the compounds studied were obtained from the temperature-dependence of KSt, according to the van’t Hoff equation. Anal. of the equilibrium and thermodn. parameters in terms of the association mechanism demonstrated the involvement of classical hydrophobic interactions in the stabilization of complexes of di- and higher alkylated uracils. Data for the derivatives substituted with polar groups proved consistent with the predominant involvement of dipole-induced dipole forces in the association This study involved multiple reactions and reactants, such as Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8HPLC of Formula: 39513-47-8).

Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.HPLC of Formula: 39513-47-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A Structure-Guided Approach to Creating Covalent FGFR Inhibitors was written by Zhou, Wenjun;Hur, Wooyoung;McDermott, Ultan;Dutt, Amit;Xian, Wa;Ficarro, Scott B.;Zhang, Jianming;Sharma, Sreenath V.;Brugge, Joan;Meyerson, Matthew;Settleman, Jeffrey;Gray, Nathanael S.. And the article was included in Chemistry & Biology (Cambridge, MA, United States) in 2010.Category: pyrimidines The following contents are mentioned in the article:

Summary: The fibroblast growth factor receptor tyrosine kinases (FGFR1, 2, 3, and 4) represent promising therapeutic targets in a number of cancers. We have developed the first potent and selective irreversible inhibitor of FGFR1, 2, 3, and 4, which we named FIIN-1 that forms a covalent bond with cysteine 486 located in the P loop of the FGFR1 ATP binding site. We demonstrated that the inhibitor potently inhibits Tel-FGFR1-transformed Ba/F3 cells (EC₅₀ = 14 nM) as well as numerous FGFR-dependent cancer cell lines. A biotin-derivatized version of the inhibitor, FIIN-1-biotin, was shown to covalently label FGFR1 at Cys486. FIIN-1 is a useful probe of FGFR-dependent cellular phenomena and may provide a starting point of the development of therapeutically relevant irreversible inhibitors of wild-type and drug-resistant forms of FGFR kinases. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Category: pyrimidines).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis was written by Leng, Xue-Yuan;Yang, Jia;Fan, Heng;Chen, Qian-Yun;Cheng, Bing-Jie;He, Hong-Xia;Gao, Fei;Zhu, Feng;Yu, Ting;Liu, Yu-Jin. And the article was included in International Immunopharmacology in 2022.Electric Literature of C22H23N5O2 The following contents are mentioned in the article:

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiol. and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of mol. biol. and immunol. techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theor. basis for understanding the pathogenesis and potential therapeutic targets of UC. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7Electric Literature of C22H23N5O2).

3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. As nucleotides in DNA and RNA, 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 C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1 was written by Yoza, Kaito;Himeno, Rika;Amano, Shinjiro;Kobashigawa, Yoshihiro;Amemiya, Shun;Fukuda, Natsuki;Kumeta, Hiroyuki;Morioka, Hiroshi;Inagaki, Fuyuhiko. And the article was included in Genes to Cells in 2016.Category: pyrimidines The following contents are mentioned in the article:

Over-expression and aberrant activation of tyrosine kinases occur frequently in human cancers. Various tyrosine kinase inhibitors (TKIs) are under clin. use, but acquisition of resistance to these drugs is a major problem. Here, we studied the interaction between two drug-resistant mutants of fibroblast growth factor receptor 1 (FGFR1), N546K and V561M, and four ATP-competitive inhibitors, ponatinib, dovitinib, PD173074 and BGJ-398. Among these protein-drug systems, the only marked reduction in affinity was that of PD173074 for the V561M mutant. We also examined the interaction of these FGFR1 variants to AMP-PNP, a nonhydrolyzable analog of ATP, and showed that N546K showed increased affinity for the ATP analog as compared with the wild type. These findings will help to clarify the mechanism of drug resistance in mutant tyrosine kinases. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Category: pyrimidines).

1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. As nucleotides in DNA and RNA, 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