Pyrimidines

《Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors》 was published in Beilstein Journal of Organic Chemistry in 2012. These research results belong to Che, Chao; Li, Song; Yang, Bo; Xin, Shengchang; Yu, Zhixiong; Shao, Taofeng; Tao, Chuanye; Lin, Shuo; Yang, Zhen. Application In Synthesis of 3-(Pyrimidin-5-yl)benzaldehyde The article mentions the following:

The previously described 3-chloro-N-[trans-4-(propylamino)cyclohexyl]-N-[[3-(4-pyridinyl)phenyl]methyl]benzo[b]thiophene-2-carboxamide [Sant-75] (I) is a newly identified potent inhibitor of the Hedgehog pathway [Smo receptor (Smoothened) antagonist]. The authors designed a diversity-oriented synthesis program and the synthesis of the target compounds (series of Sant-75 analogs) was achieved, which lays a foundation for further investigation of the structure-activity relationship of this important class of hedgehog-pathway inhibitors. The results came from multiple reactions, including the reaction of 3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6Application In Synthesis of 3-(Pyrimidin-5-yl)benzaldehyde)

3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6) 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 In Synthesis of 3-(Pyrimidin-5-yl)benzaldehyde

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of C11H8N2O4On May 1, 2018 ,《Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “”Freeze”” the pre-translocated complex during the polymerization catalytic cycle》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Lacbay, Cyrus M.; Menni, Michael; Bernatchez, Jean A.; Gotte, Matthias; Tsantrizos, Youla S.. The article conveys some information:

Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the byproduct of nucleotide incorporation. Small mols. were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex. In the experiment, the researchers used 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Synthetic Route of C11H8N2O4)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) 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 C11H8N2O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 944401-55-2On September 14, 2017 ,《5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology》 was published in Journal of Medicinal Chemistry. The article was written by Beaufils, Florent; Cmiljanovic, Natasa; Cmiljanovic, Vladimir; Bohnacker, Thomas; Melone, Anna; Marone, Romina; Jackson, Eileen; Zhang, Xuxiao; Sele, Alexander; Borsari, Chiara; Mestan, Jurgen; Hebeisen, Paul; Hillmann, Petra; Giese, Bernd; Zvelebil, Marketa; Fabbro, Doriano; Williams, Roger L.; Rageot, Denise; Wymann, Matthias P.. The article contains the following contents:

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclin. characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1 as a clin. candidate with a broad application range in oncol., including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clin. trials for advanced solid tumors and refractory lymphoma. In the experiment, the researchers used many compounds, for example, 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2SDS of cas: 944401-55-2)

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(cas: 944401-55-2) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. SDS of cas: 944401-55-2They 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

Hu, Zongyi; Lan, Keng-Hsin; He, Shanshan; Swaroop, Manju; Hu, Xin; Southall, Noel; Zheng, Wei; Liang, T. Jake published an article on February 28 ,2014. The article was titled 《Novel cell-based hepatitis C virus infection assay for quantitative high-throughput screening of anti-hepatitis C virus compounds》, and you may find the article in Antimicrobial Agents and Chemotherapy.Recommanded Product: 213743-31-8 The information in the text is summarized as follows:

Therapy for hepatitis C virus (HCV) infection has advanced with the recent approval of direct-acting antivirals in combination with peginterferon and ribavirin. New antivirals with novel targets are still needed to further improve the treatment of hepatitis C. Previously reported screening methods for HCV inhibitors either are limited to a virus-specific function or apply a screening method at a single dose, which usually leads to high false-pos. or -neg. rates. We developed a quant. high-throughput screening (qHTS) assay platform with a cell-based HCV infection system. This highly sensitive assay can be miniaturized to a 1,536-well format for screening of large chem. libraries. All candidates are screened over a 7-concentration dose range to give EC50s (compound concentrations at 50% efficacy) and dose-response curves. Using this assay format, we screened a library of pharmacol. active compounds (LOPAC). Based on the profile of dose-dependent curves of HCV inhibition and cytotoxicity, 22 compounds with adequate curves and EC50s of <10 μM were selected for validation. In two addnl. independent assays, 17 of them demonstrated specific inhibition of HCV infection. Ten potential candidates with efficacies of >70% and CC50s (compound concentrations at 50% cytotoxicity) of <30 μM from these validated hits were characterized for their target stages in the HCV replication cycle. In this screen, we identified both known and novel hits with diverse structural and functional features targeting various stages of the HCV replication cycle. The pilot screen demonstrates that this assay system is highly robust and effective in identifying novel HCV inhibitors and that it can be readily applied to large-scale screening of small-mol. libraries. After reading the article, we found that the author used 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Recommanded Product: 213743-31-8)

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) 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.Recommanded Product: 213743-31-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Palomino, Eduardo; Meltsner, Bernard R.; Kessel, David; Horwitz, Jerome P. published an article on January 31 ,1990. The article was titled 《Synthesis and in vitro evaluation of some modified 4-thiopyrimidine nucleosides for prevention or reversal of AIDS – associated neurological disorders》, and you may find the article in Journal of Medicinal Chemistry.Application In Synthesis of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate The information in the text is summarized as follows:

Oxygen-sulfur exchange at the C-4 carbonyl of several modified pyrimidine nucleosides, including 3′-azido-3′-deoxythymidine (AZT), is described in an effort to enhance the lipophilicity and, thereby, the delivery to the central nervous system of the sulfur analogs without compromising the anti-HIV activities of the parental structures. Preparation of 3′-azido-3′-deoxy-4-thiothymidine (I) proceeded from 4-thiothymidine and utilized the same methodol. developed for the initial synthesis of AZT. Thiation of 2′,3′-didehydro-3′-deoxythymidine and 2′,3′-didehydro-2′,3′-dideoxyuridine was carried out with Lawesson’s reagent on the corresponding 5′-O-benzoate esters. The products on alk. hydrolysis gave 2′,3′-didehydro-3′-deoxy-4-thiothymidine and 2′,3′-didehydro-2′,3′-dideoxy-4-uridine (III). The same series of reactions were applied to the 5′-O-benzoate esters of 2′,3′-dideoxyuridine and 3′-deoxythymidine to give 2′,3′-dideoxy-4-thiouridine (IV) and 3′-deoxy-4-thiothymidine (V). Characterization of the saturated and unsaturated thionucleosides included mass spectrometric studies. Under electron impact conditions, the thiated analogs gave more intense parent ions than the corresponding oxygen precursors. The lipophilicity of thymidine and the 3′-deoxythymidine derivatives are enhanced significantly, as indicated, by increases in corresponding P values (1-octanol-0.1M sodium phosphate) upon replacement of the 4-carbonyl oxygens by sulfur. II, III, IV, and V were evaluated for their effects on HIV-induced cytopathogenicity of MT-2 and CEM cells. Only II and V were moderately active in protecting both cell lines against the cytolytic effect of HIV. The inhibitory effects of II-V on thymidine phosphorylation by rabbit thymus thymidine kinase were evaluated. Only I showed moderate affinity (Ki = 54 μM) for the enzyme. The generally weak anti-HIV activities of the remaining thio analogs are consistent with correspondingly low susceptibilities to thymidine kinase phosphorylation as estimated from the resp. Ki values of the synthetic nucleosides. However, the phosphorylation of the 5′-monophosphate derivatives to their resp. 5′-triphosphates must also be considered in connection with the weak in vitro anti-HIV effects of these thiated compounds The experimental process involved the reaction of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Application In Synthesis of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate)

((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9) 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 In Synthesis of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Tian, Chao; Han, Zifei; Li, Yuanxin; Wang, Meng; Yang, Jiajia; Wang, Xiaowei; Zhang, Zhili; Liu, Junyi published 《Synthesis and biological evaluation of 2,6-disubstituted-9H-purine, 2,4-disubstituted-thieno[3,2-d]pyrimidine and -7H-pyrrolo[2,3-d]pyrimidine analogues as novel CHK1 inhibitors》.European Journal of Medicinal Chemistry published the findings.Recommanded Product: 90213-66-4 The information in the text is summarized as follows:

Arylamino imidazopyrimidines, thienopyrimidines, and pyrrolopyrimidines such as I were prepared as inhibitors of checkpoint kinase 1 (CHK1) for potential use as antitumor agents. I exhibited low anti-proliferative effects towards HT29 and Hek293 cell lines, potentiated the antitumor activity of gemcitabine in HT29 cells, and was selective for CHK1 over a panel of fourteen other kinases. I induced S phase accumulation in gemcitabine-treated HT29 cells. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Recommanded Product: 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. Recommanded Product: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Journal of Medicinal Chemistry included an article by Vazquez, Michael L.; Kaila, Neelu; Strohbach, Joseph W.; Trzupek, John D.; Brown, Matthew F.; Flanagan, Mark E.; Mitton-Fry, Mark J.; Johnson, Timothy A.; TenBrink, Ruth E.; Arnold, Eric P.; Basak, Arindrajit; Heasley, Steven E.; Kwon, Soojin; Langille, Jonathan; Parikh, Mihir D.; Griffin, Sarah H.; Casavant, Jeffrey M.; Duclos, Brian A.; Fenwick, Ashley E.; Harris, Thomas M.; Han, Seungil; Caspers, Nicole; Dowty, Martin E.; Yang, Xin; Banker, Mary Ellen; Hegen, Martin; Symanowicz, Peter T.; Li, Li; Wang, Lu; Lin, Tsung H.; Jussif, Jason; Clark, James D.; Telliez, Jean-Baptiste; Robinson, Ralph P.; Unwalla, Ray. Related Products of 90213-66-4. The article was titled 《Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases》. The information in the text is summarized as follows:

Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. The authors’ efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, the authors discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by x-ray crystallog. anal. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clin. candidate for the treatment of JAK1-mediated autoimmune diseases.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 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. Related Products of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration》 were Cao, Hengyi; Zhu, Guangya; Sun, Lin; Chen, Ge; Ma, Xinxin; Luo, Xiao; Zhu, Jidong. And the article was published in European Journal of Medicinal Chemistry in 2019. Application of 3764-01-0 The author mentioned the following in the article:

Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5, (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(7-(trifluoromethyl)4,5-dihydroimidazo[1,5-a]quinolin-3-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one [2379528-08-0], exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclin. candidate to treat IDH1-mutant brain tumors. In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0) was used in this study.

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3》 were Li, Yingxiu; Ye, Tianyu; Xu, Le; Dong, Yuhong; Luo, Yong; Wang, Chu; Han, Yufei; Chen, Ke; Qin, Mingze; Liu, Yajing; Zhao, Yanfang. And the article was published in European Journal of Medicinal Chemistry in 2019. Reference of 2,4-Dichloropyrimidine The author mentioned the following in the article:

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “”A”” Ph ring and “”B”” Ph ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor. After reading the article, we found that the author used 2,4-Dichloropyrimidine(cas: 3934-20-1Reference of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Reference of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Discovery of potent, orally bioavailable ERK1/2 inhibitors with isoindolin-1-one structure by structure-based drug design》 were Ji, Dezhong; Zhang, Lingzhi; Zhu, Qihua; Bai, Ying; Wu, Yaoyao; Xu, Yungen. And the article was published in European Journal of Medicinal Chemistry in 2019. Category: pyrimidines The author mentioned the following in the article:

Constitutive activation of MAPK (RAS/RAF/MEK/ERK) pathway is frequently observed in many tumors and thus has become an interesting therapeutic target for cancer therapy. Despite the successful development of BRAF and MEK inhibitors in clinic treatment, resistance often appears to re-enhance ERK1/2 signaling. Inspired by the central role of the ERK1/2 signaling cascade in cancer, we describe the scaffold-hopping generation of a series of isoindolin-1-one ERK1/2 inhibitors. Our new compounds could inhibit proliferation of KRAS and BRAF mutant cells lines at low nanomolar concentrations Compound 22a possesses acceptable pharmacokinetic profiles and showed considerable in vivo antitumor efficacy in a HCT-116 xenograft model, providing a promising basis for further optimization towards clin. ERK1/2 inhibitors. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloropyrimidine(cas: 3934-20-1Category: pyrimidines)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia