Pyrimidines

Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase was written by Guagnano, Vito;Furet, Pascal;Spanka, Carsten;Bordas, Vincent;Le Douget, Mickael;Stamm, Christelle;Brueggen, Josef;Jensen, Michael R.;Schnell, Christian;Schmid, Herbert;Wartmann, Markus;Berghausen, Joerg;Drueckes, Peter;Zimmerlin, Alfred;Bussiere, Dirksen;Murray, Jeremy;Graus Porta, Diana. And the article was included in Journal of Medicinal Chemistry in 2011.Computed Properties of C28H41N7O3 The following contents are mentioned in the article:

A novel series of N-aryl-N’-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent. 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: 219580-11-7Computed Properties of C28H41N7O3).

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 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.Computed Properties of C28H41N7O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of JMJD6 by 2-Oxoglutarate Mimics was written by Islam, Sailful Md.;Thinnes, Cyrille C.;Holt-Martyn, James P.;Chowdhury, Rasheduzzaman;McDonough, Michael A.;Schofield, Christopher J.. And the article was included in ChemMedChem in 2022.Synthetic Route of C22H23N5O2 The following contents are mentioned in the article:

Studies on the inhibition of the human 2-oxoglutarate dependent oxygenase JMJD6, which is a cancer target, by 2-oxoglutarate mimics / competitors, including human drugs, drug candidates, and metabolites relevant to cancer are described. JMJD6 assays employed NMR to monitor inhibitor binding and use of mass spectrometry to monitor JMJD6-catalyzed lysine hydroxylation. Notably, some clin. applied prolyl hydroxylase inhibitors also inhibit JMJD6. The results will help enable the development of inhibitors selective for human oxygenases, including JMJD6. 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: 1373422-53-7Synthetic Route 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 derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Synthetic Route of C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Identification of the KDM2/7 Histone Lysine Demethylase Subfamily Inhibitor and its Antiproliferative Activity was written by Suzuki, Takayoshi;Ozasa, Hiroki;Itoh, Yukihiro;Zhan, Peng;Sawada, Hideyuki;Mino, Koshiki;Walport, Louise;Ohkubo, Rei;Kawamura, Akane;Yonezawa, Masato;Tsukada, Yuichi;Tumber, Anthony;Nakagawa, Hidehiko;Hasegawa, Makoto;Sasaki, Ryuzo;Mizukami, Tamio;Schofield, Christopher J.;Miyata, Naoki. And the article was included in Journal of Medicinal Chemistry in 2013.Computed Properties of C22H23N5O2 The following contents are mentioned in the article:

Histone N^ε-Me lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogs bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC₅₀s of 6.8, 0.2, and 1.2 μM, resp. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents. 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: 1373422-53-7Computed Properties 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 ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. 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.Computed Properties of C22H23N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Functionally defined therapeutic targets in diffuse intrinsic pontine glioma was written by Grasso, Catherine S.;Tang, Yujie;Truffaux, Nathalene;Berlow, Noah E.;Liu, Lining;Debily, Marie-Anne;Quist, Michael J.;Davis, Lara E.;Huang, Elaine C.;Woo, Pamelyn J.;Ponnuswami, Anitha;Chen, Spenser;Johung, Tessa B.;Sun, Wenchao;Kogiso, Mari;Du, Yuchen;Qi, Lin;Huang, Yulun;Hutt-Cabezas, Marianne;Warren, Katherine E.;Le Dret, Ludivine;Meltzer, Paul S.;Mao, Hua;Quezado, Martha;van Vuurden, Dannis G.;Abraham, Jinu;Fouladi, Maryam;Svalina, Matthew N.;Wang, Nicholas;Hawkins, Cynthia;Nazarian, Javad;Alonso, Marta M.;Raabe, Eric H.;Hulleman, Esther;Spellman, Paul T.;Li, Xiao-Nan;Keller, Charles;Pal, Ranadip;Grill, Jacques;Monje, Michelle. And the article was included in Nature Medicine (New York, NY, United States) in 2015.Computed Properties of C24H27N5O2 The following contents are mentioned in the article:

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chem. screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Computed Properties of C24H27N5O2).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Computed Properties of C24H27N5O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fast in-vitro screening of FLT3-ITD inhibitors using silkworm-baculovirus protein expression system was written by Yamamoto, Naoki;Kikuchi, Jiro;Furukawa, Yusuke;Shibayama, Naoya. And the article was included in PLoS One in 2022.Name: 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:

We report expression and purification of a FLT3 protein with ITD mutation (FLT3-ITD) with a steady tyrosine kinase activity using a silkworm-baculovirus system, and its application as a fast screening system of tyrosine kinase inhibitors. The FLT3-ITD protein was expressed in Bombyx mori L. pupae infected by gene-modified nucleopolyhedrovirus, and was purified as an active state. We performed an inhibition assay using 17 kinase inhibitors, and succeeded in screening two inhibitors for FLT3-ITD. The result has paved the way for screening FLT3-ITD inhibitors in a fast and easy manner, and also for structural studies. 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: 219580-11-7Name: 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. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Name: 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

Feedback Activation of STAT3 Is a Widespread Drug-Resistance Mechanism was written by Anonymous. And the article was included in Cancer Discovery in 2014.Reference of 219580-11-7 The following contents are mentioned in the article:

STAT3 activation contributes to resistance to a broad spectrum of targeted therapies in cancer. Receptor tyrosine kinase (RTK)/MEK inhibition induces autocrine STAT3 activation through FGFR and JAK kinases. Together with the observation that high STAT3 and FGFR expression was associated with poor response to EGFR-targeted therapy in a small group of patients with non-small cell lung cancer (NSCLC), these findings implicate feedback upregulation of STAT3 as a common cause of resistance to RTK/MEK-targeted therapy and provide a rationale for combination strategies including inhibitors of STAT3 or its upstream 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: 219580-11-7Reference of 219580-11-7).

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. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Reference of 219580-11-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis in the heterocyclic series. IX. Syntheses and reactions of 4,6-disubstituted pyrimidine-5-aldehydes was written by Bredereck, Hellmut;Simchen, Gerhard;Santos, Antonio A.. And the article was included in Chemische Berichte in 1967.HPLC of Formula: 14160-85-1 The following contents are mentioned in the article:

cf. CA 66, 94992n. In the reactions of dihydroxypyrimidines with Vilsmeier reagents, uracil gave (Me2N+:CHNHCOCH:CHOH)Cl-, and 4-hydroxy-6-oxodihydropyrimidines (I, R = H, Me, or Ph) were formylated at their 5-position to give 4-hydroxy-6-oxo-5-dimethylaminomethylene-5,6-dihydropyrimidine-HCl derivatives (II) which were converted, by POCl3/PhNMe2, into 4,6-dichloro-5-formylpyrimidine derivatives (III). III were converted, by nucleophilic agents (RR’NH or MeNH2), into 4-amino-6-chloro-5-formylpyrimidine derivatives (IV, R = H, Me, or Ph, R’ = H or Me) or 4,6-bis(methylamino)-5-methylaminomethylenepyrimidine. II were treated with Et malonate to give 7H-pyrano[2,3-d]pyrimidine derivatives (V). This study involved multiple reactions and reactants, such as 4,6-Dihydroxy-2-methylpyrimidine-5-carbaldehyde (cas: 14160-85-1HPLC of Formula: 14160-85-1).

4,6-Dihydroxy-2-methylpyrimidine-5-carbaldehyde (cas: 14160-85-1) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.HPLC of Formula: 14160-85-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of a viral prolyl hydroxylase was written by Langley, Gareth W.;Abboud, Martine I.;Lohans, Christopher T.;Schofield, Christopher J.. And the article was included in Bioorganic & Medicinal Chemistry in 2019.Application In Synthesis 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:

The hydroxylation of prolyl-residues in eukaryotes is important in collagen biosynthesis and in hypoxic signalling. The hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are drug targets for the treatment of anemia, while the procollagen prolyl hydroxylases and other 2-oxoglutarate dependent oxygenases are potential therapeutic targets for treatment of cancer, fibrotic disease, and infection. We describe assay development and inhibition studies for a procollagen prolyl hydroxylase from Paramecium bursaria chlorella virus 1 (vCPH). The results reveal HIF PHD inhibitors in clin. trials also inhibit vCPH. Implications for the targeting of the human PHDs and microbial prolyl hydroxylases are discussed. 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: 1373422-53-7Application In Synthesis 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. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Application In Synthesis 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

Preparation of pyrimidine isocyanates was written by Dyer, Elizabeth;Nycz, Thomas J.;Long, Michael B.. And the article was included in Journal of Heterocyclic Chemistry in 1972.Application of 39513-47-8 The following contents are mentioned in the article:

Uracil-5-yl isocyanate and 1,3-dimethyluracil-5-yl isocyanate were prepared from the corresponding new carboazides. 1,3-Dimethyluracil-5-ylmethyl isocyanate obtained from the chloro compound and silver cyanate, was polymerized with an anionic initiator to the cyclic trimer. Attempts to isolate uracil-6-yl isocyanate, 1,3-dimethyluracil-6-yl isocyanate, 4-pyrimidinyl isocyanate, and 2,6-dichloro-4-pyrimidinyl isocyanate were unsuccessful. Ethyl carbamate derivatives were made from all new azides and isocyanates. Other new pyrimidine derivatives included N,N’-bis(4-pyrimidinylcarbonyl)hydrazine, N,N’-bis(1,3-dimethyluracil-5-yl)urea, N,N’-bis(1,3-dimethyluracil-6-yl)urea, and N,N’-bis(2,5,-6,-trichloro-4-pyrimidinyl)oxamide. This study involved multiple reactions and reactants, such as Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (cas: 39513-47-8Application of 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. 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. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Application of 39513-47-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Inhibition of demethylases by GSK-J1/J4 was written by Heinemann, Bo;Nielsen, Jesper Morten;Hudlebusch, Heidi Rye;Lees, Michael J.;Larsen, Dorthe Vang;Boesen, Thomas;Labelle, Marc;Gerlach, Lars-Ole;Birk, Peter;Helin, Kristian. And the article was included in Nature (London, United Kingdom) in 2014.Reference of 1373423-53-0 The following contents are mentioned in the article:

The recent publication, by Kruidenier, L. etal. ibid 488 (2012), of the first highly potent and specific inhibitor GSK-J1/J4 of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A provides a potential tool compound for this histone demethylase subfamily. The inhibitor is not specific for the H3K27me3/me2-demethylase subfamily in vitro and in tissue culture assays. Thus, the inhibitor cannot be used alone for drawing conclusions regarding the specific role of H3K27me3/me2-demethylase activity in biol. processes or disease. The authors’ results show that GSK-J1 and GSK-J4 inhibit demethylases in addition to KDM6B and KDM6A. Therefore, this compound cannot be used alone for demonstrating a role for H3K27 demethylation in biol. processes. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Reference of 1373423-53-0).

Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Reference of 1373423-53-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia