Day: October 20, 2022

Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylateOn March 9, 2006, Koch, Uwe; Attenni, Barbara; Malancona, Savina; Colarusso, Stefania; Conte, Immacolata; Di Filippo, Marcello; Harper, Steven; Pacini, Barbara; Giomini, Claudia; Thomas, Steven; Incitti, Ilario; Tomei, Licia; De Francesco, Raffaele; Altamura, Sergio; Matassa, Victor G.; Narjes, Frank published an article in Journal of Medicinal Chemistry. The article was 《2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase: Discovery, SAR, Modeling, and Mutagenesis》. The article mentions the following:

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. The authors recently disclosed dihydroxypyrimidine carboxylates as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as (I) (EC50 9.3 μM), which now show activity in the cell-based HCV replication assay. The structure-activity relation of these inhibitors is discussed in the context of their physicochem. properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions. In addition to this study using Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate, there are many other studies that have used Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6Application In Synthesis of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate) was used in this study.

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) 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 Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Nucleic Acids Research included an article by Baddock, Hannah T.; Brolih, Sanja; Yosaatmadja, Yuliana; Ratnaweera, Malitha; Bielinski, Marcin; Swift, Lonnie P.; Cruz-Migoni, Abimael; Fan, Haitian; Keown, Jeremy R.; Walker, Alexander P.; Morris, Garrett M.; Grimes, Jonathan M.; Fodor, Ervin; Schofield, Christopher J.; Gileadi, Opher; McHugh, Peter J.. Electric Literature of C11H8N2O4. The article was titled 《Characterization of the SARS-CoV-2 ExoN (nsp14ExoN-nsp10) complex: implications for its role in viral genome stability and inhibitor identification》. The information in the text is summarized as follows:

The SARS-CoV-2 coronavirus is the causal agent of the current global pandemic. SARS-CoV-2 belongs to an order, Nidovirales, with very large RNA genomes. It is proposed that the fidelity of coronavirus (CoV) genome replication is aided by an RNA nuclease complex, comprising the non-structural proteins 14 and 10 (nsp14-nsp10), an attractive target for antiviral inhibition. Our results validate reports that the SARS-CoV-2 nsp14-nsp10 complex has RNase activity. Detailed functional characterization reveals nsp14-nsp10 is a versatile nuclease capable of digesting a wide variety of RNA structures, including those with a blocked 3′-terminus. Consistent with a role in maintaining viral genome integrity during replication, we find that nsp14-nsp10 activity is enhanced by the viral RNA-dependent RNA polymerase complex (RdRp) consisting of nsp12-nsp7-nsp8 (nsp12-7-8) and demonstrate that this stimulation is mediated by nsp8. We propose that the role of nsp14-nsp10 in maintaining replication fidelity goes beyond classical proofreading by purging the nascent replicating RNA strand of a range of potentially replication-terminating aberrations. Using our developed assays, we identify drug and drug-like mols. that inhibit nsp14-nsp10, including the known SARS-CoV-2 major protease (Mpro) inhibitor ebselen and the HIV integrase inhibitor raltegravir, revealing the potential for multifunctional inhibitors in COVID-19 treatment. The experimental process involved the reaction of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2Electric Literature of C11H8N2O4)

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

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Murthy Bandaru, Siva Sankar; Bhilare, Shatrughn; Chrysochos, Nicolas; Gayakhe, Vijay; Trentin, Ivan; Schulzke, Carola; Kapdi, Anant R. published 《Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes》.Organic Letters published the findings.Quality Control of 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib intermediate as well as the formal synthesis of Alogliptin in competitive yields. The experimental part of the paper was very detailed, including the reaction process of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Quality Control of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Quality Control of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Journal of Medicinal Chemistry included an article by Huang, Boshi; Chen, Wenmin; Zhao, Tong; Li, Zhenyu; Jiang, Xiangyi; Ginex, Tiziana; Vilchez, David; Luque, Francisco Javier; Kang, Dongwei; Gao, Ping; Zhang, Jian; Tian, Ye; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. Safety of 2,4-Dichloropyrimidine. The article was titled 《Exploiting the Tolerant Region I of the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Binding Pocket: Discovery of Potent Diarylpyrimidine-Typed HIV-1 NNRTIs against Wild-Type and E138K Mutant Virus with Significantly Improved Water Solubility and Favorable Safety Profiles》. The information in the text is summarized as follows:

Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility In the present work, hydrophilic morpholine or methylsulfonyl and sulfamide-substituted piperazine/piperidines were introduced into the right wing of DAPYs targeting the solvent-exposed tolerant region I. The anti-HIV-1 activities of 11c (EC50(WT) = 0.0035 μM, EC50(E138K) = 0.0075 μM) were the same as and 2-fold better than that of the lead etravirine against the wild-type and E138K mutant HIV-1, resp., with a relative low cytotoxicity (CC50 ≥ 173 μM). Further test showed a significant improvement in the water solubility of 11c. Besides, 11c displayed no significant inhibition on main cytochrome P 450 enzymes and exhibited no acute/subacute toxicities at doses of 2000 mg·kg-1/50 mg·kg-1 in mice. Taken together, we consider that 11c is a promising lead for further structural optimization. The results came from multiple reactions, including the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Safety 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.Safety of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Wang, Junwei; Li, Hui; He, Guangchao; Chu, Zhaoxing; Peng, Kewen; Ge, Yiran; Zhu, Qihua; Xu, Yungen. Safety of 2,4,6-Trichloropyrimidine The article mentions the following:

Concomitant inhibition of PARP and PI3K pathways has been recognized as a promising strategy for cancer therapy, which may expand the clin. utility of PARP inhibitors. Herein, we report the discovery of dual PARP/PI3K inhibitors that merge the pharmacophores of PARP and PI3K inhibitors. Among them, compound 15 stands out as the most promising candidate with potent inhibitory activities against both PARP-1/2 and PI3Kα/δ with pIC50 values greater than 8. Compound 15 displayed superior antiproliferative profiles against both BRCA-deficient and BRCA-proficient cancer cells in cellular assays. The prominent synergistic effects produced by the concomitant inhibition of the two targets were elucidated by comprehensive biochem. and cellular mechanistic studies. In vivo, 15 showed more efficacious antitumor activity than the corresponding drug combination (Olaparib + BKM120) in the MDA-MB-468 xenograft model with a tumor growth inhibitory rate of 73.4% without causing observable toxic effects. All of the results indicate that 15, a first potent dual PARP/PI3K inhibitor, is a highly effective anticancer compound In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Safety of 2,4,6-Trichloropyrimidine) was used in this study.

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Safety of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application In Synthesis of 2,4-DichloropyrimidineIn 2019 ,《Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Yu, Ru-Nan; Chen, Cheng-Juan; Shu, Lei; Yin, Yuan; Wang, Zhi-Jian; Zhang, Tian-Tai; Zhang, Da-Yong. The article conveys some information:

Janus kinases (JAKs) play a key role in the proliferation, apoptosis and differentiation of immune cells, and JAKs are considered as an attractive target for the treatment of inflammatory and autoimmune diseases. Here we show the design and optimization of pyrimidine-4,6-diamine derivatives as selectivity JAK3 inhibitors. Compound I, which might interact with unique cysteine (Cys909) residue in JAK3, exhibited excellent JAK3 inhibitory activity (IC50 = 2.1 nM) and high JAK kinase selectivity. In cellular assay, I showed moderate potency inhibiting IL-2-stimulated T cell proliferation. The data supports the further development of novel JAKs inhibitors. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Application In Synthesis of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Application In Synthesis of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Quality Control of 2,4,6-TrichloropyrimidineIn 2015 ,《Design, synthesis, and biological evaluation of pyrimidine-2-carboxamide analogs: investigation for novel RAGE inhibitors with reduced hydrophobicity and toxicity》 appeared in Archives of Pharmacal Research. The author of the article were Kim, Seok-Ho; Han, Young Taek. The article conveys some information:

This paper describes an investigation of novel RAGE inhibitors with improved drug-like properties. To identify the improved drug-like RAGE inhibitor, the authors designed and synthesized pyrimidine-2-carboxamide analogs based on the previous work. Several potent analogs with improved hydrophilicity were identified by evaluation of RAGE inhibitory activity. In particular, one of the potent (diethylamino)ethoxymethoxy analogs did not exhibit undesired cytotoxicity in contrast with the parent RAGE inhibitors. In the experimental materials used by the author, we found 2,4,6-Trichloropyrimidine(cas: 3764-01-0Quality Control of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Quality Control of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies》 was written by Huang, Ying; Sendzik, Martin; Zhang, Jeff; Gao, Zhenting; Sun, Yongfeng; Wang, Long; Gu, Justin; Zhao, Kehao; Yu, Zhengtian; Zhang, Lijun; Zhang, Qiong; Blanz, Joachim; Chen, Zijun; Dubost, Valerie; Fang, Douglas; Feng, Lijian; Fu, Xingnian; Kiffe, Michael; Li, Ling; Luo, Fangjun; Luo, Xiao; Mi, Yuan; Mistry, Prakash; Pearson, David; Piaia, Alessandro; Scheufler, Clemens; Terranova, Remi; Weiss, Andreas; Zeng, Jue; Zhang, Hailong; Zhang, Jiangwei; Zhao, Mengxi; Dillon, Michael P.; Jeay, Sebastien; Qi, Wei; Moggs, Jonathan; Pissot-Soldermann, Carole; Li, En; Atadja, Peter; Lingel, Andreas; Oyang, Counde. Application of 69696-35-1 And the article was included in Journal of Medicinal Chemistry on April 14 ,2022. The article conveys some information:

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a mol. level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-mol.-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models. Here, we report the stepwise optimization of the tool compound EED226 toward the potent and selective EED inhibitor MAK683 (compound 22) and its subsequent preclin. characterization. Based on a balanced PK/PD profile, efficacy, and mitigated risk of forming reactive metabolites, MAK683 has been selected for clin. development.5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1Application of 69696-35-1) was used in this study.

5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Application of 69696-35-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Extrusion of sulfur from [(acylmethyl)thio]pyrimidinones》 was written by Roth, Barbara; Laube, Renee; Tidwell, Mary Y.; Rauckman, Barbara S.. Category: pyrimidines And the article was included in Journal of Organic Chemistry on August 29 ,1980. The article conveys some information:

Thermally mediated S extrusion from the (phenacylthio)pyrimidinones I (R = H, R1 = Br, H, MeO; R = Me, R1 = Br) occurs rapidly in solution at 125° to yield the (benzoylmetheylene)pyrimidinones II. However, III rearranges via an episulfide intermediate to IV. Adjacent 3- or 5-Me substituents in the pyrimidine ring assist S extrusion. No reaction occurs in the absence of a 2-oxo function or on replacement of it by a 2-amino group. On the other hand, 2-amino-4[(1-methylacetonyl)thio]-6(1H)-pyrimidinone cyclizes very readily to give the thieno pyrimidinone V. 2-(Phenacylthio)-4(3H)-pyrimidinones lose S at about one-seventh the rate of the 4-phenacylthio isomers. No thermally mediated reaction occurs with 2-(acetonylthio)-4-pyrimidinones under the conditions described here. In the part of experimental materials, we found many familiar compounds, such as 2-Methoxy-4-methylpyrimidine(cas: 14001-60-6Category: pyrimidines)

2-Methoxy-4-methylpyrimidine(cas: 14001-60-6) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《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