Category: pyrimidines

Application In Synthesis of 2,4-DichloropyrimidineIn 2021 ,《Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies》 was published in Journal of Medicinal Chemistry. The article was written by Huang, Jianhang; Wang, Xinren; Dong, Ruinan; Liu, Xiaoyue; Li, Hongmei; Zhang, Tianyi; Xu, Junyu; Liu, Chenhe; Zhang, Yanmin; Hou, Shaohua; Tang, Weifang; Lu, Tao; Chen, Yadong. The article contains the following contents:

Hematol. malignancies (HM) start in blood forming tissue or in the cells of the immune system. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them control cellular transcription. CDK inhibition can trigger apoptosis and could be particularly useful in hematol. malignancies. Herein, we describe our efforts toward the discovery of a novel series of quinazoline derivatives as CDK inhibitors. Intensive structural modifications lead to the identification of compound 37d as the most active inhibitors of CDKs 1, 2, 4, 8 and 9 with balancing potency and selectivity against CDKs. Further biol. studies revealed that compound 37d can arrest the cell cycle and induce apoptosis via activating PARP and caspase 3. More importantly, compound 37d showed good antitumor efficacy in multiple HM mice xenograft models with no obvious toxicity. These results indicated that CDK 1, 2, 4, 8, and 9 inhibitors could be potentially used to treat certain hematol. malignancies. In the experiment, the researchers used 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

COA of Formula: C4H2Cl2N2In 2019 ,《Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of non-small cell lung cancer》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Wang, Xueyuan; Bai, Enhe; Zhou, Hui; Sha, Sijia; Miao, Hang; Qin, Yanru; Liu, Zhaogang; Wang, Jia; Zhang, Haoyang; Lei, Meng; Liu, Jia; Hai, Ou; Zhu, Yongqiang. The article conveys some information:

Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new mol. entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymic inhibitory activity (IC50, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC50, 1.61 μM). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, resp. and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for i.v. treatment of non-small cell lung cancer. In the experiment, the researchers used many compounds, for example, 2,4-Dichloropyrimidine(cas: 3934-20-1COA of Formula: C4H2Cl2N2)

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.COA of Formula: C4H2Cl2N2

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

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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

Meng, Fan-Jie; Shao, Bing-Ru; Velopolcek, Maria K.; Guo, Xuan; Feng, Guang-Shou; Shi, Lei published their research in Organic & Biomolecular Chemistry in 2021. The article was titled 《Redox deracemization of phosphonate-substituted dihydropyrimidines》.Name: 2,4-Dichloropyrimidine The article contains the following contents:

An efficient redox deracemization of the phosphonic ester substituted 3,4-dihydropyrimidin-2-one (DHPM) derivatives I (R = Ph, Me, naphth-2-yl, etc.; R1 = H, Me, Ph) is described. The one-pot deracemization strategy consisted of the oxidization to destroy the stereocenter center and the following asym. transfer hydrogenation to regenerate the chiral carbon center with the vicinal phosphonic ester group, providing a series of optically active phosphonate substituted DHPMs with up to 96% ee. The results came from multiple reactions, including the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Name: 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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.Name: 2,4-Dichloropyrimidine

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Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Brawn, Ryan A.; Cook, Andrew; Omoto, Kiyoyuki; Ke, Jiyuan; Karr, Craig; Colombo, Federico; Virrankoski, Milena; Prajapati, Sudeep; Reynolds, Dominic; Bolduc, David M.; Nguyen, Tuong-Vi; Gee, Patricia; Borrelli, Deanna; Caleb, Benjamin; Yao, Shihua; Irwin, Sean; Larsen, Nicholas A.; Selvaraj, Anand; Zhao, Xuesong; Ioannidis, Stephanos published their research in ACS Medicinal Chemistry Letters in 2021. The article was titled 《Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3》.Product Details of 3764-01-0 The article contains the following contents:

Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clin. trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR anal. and structure-based drug design led to analogs with improved potency and drug metabolism and pharmacokinetics properties. The results came from multiple reactions, including the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Product Details of 3764-01-0)

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.Product Details of 3764-01-0

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Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Reactions of pyrimidin-5-yllithium compounds》 were Caton, M. P. L.; Grant, M. S.; Pain, D. L.; Slack, R.. And the article was published in Journal of the Chemical Society in 1965. Category: pyrimidines The author mentioned the following in the article:

Pyrimidin-5-yllithium compounds, mostly having alkoxy substituents, reacted with CO2, HCONMe2, and S, forming, resp., carboxylic acids, aldehydes, and polysulfides. The last were reduced and converted in situ into (pyrimidin-5-ylthio)alkanoic acids. Preparations of pyrimidin-5-ylacetic acids and of 5-bromo-2-formylpyrimidine are also described. The experimental process involved the reaction of 5-Bromo-4,6-dimethoxy-2-methylpyrimidine(cas: 4319-83-9Category: pyrimidines)

5-Bromo-4,6-dimethoxy-2-methylpyrimidine(cas: 4319-83-9) 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

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Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Edo, Kiyoto; Sakamoto, Takao; Yamanaka, Hiroshi published their research in Chemical & Pharmaceutical Bulletin on December 31 ,1978. The article was titled 《Studies on pyrimidine derivatives. IX. Coupling reaction of mono-substituted acetylenes with iodopyrimidines》.Synthetic Route of C6H6BrClN2 The article contains the following contents:

Pyrimidine derivatives containing an acetylenic side chain were prepared by reaction of alkyl or Ph acetylenes with 2-, 4-, and 5-iodopyrimidines in the presence of Pd(PPh3)2Cl2. When HCCCH2OH was used, the reaction yield decreased. The reaction proceeded with 2,4-diiodo- and 4,6-diiodopyrimidines to give dialkynyl derivatives This acetylene coupling reaction was applicable to the preparation of 4-quinazoline derivatives The results came from multiple reactions, including the reaction of 5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1Synthetic Route of C6H6BrClN2)

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.Synthetic Route of C6H6BrClN2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

COA of Formula: C11H8N2O4On October 21, 2004 ,《HCV NS5b RNA-Dependent RNA Polymerase Inhibitors: From α,γ-Diketoacids to 4,5-Dihydroxypyrimidine- or 3-Methyl-5- hydroxypyrimidinonecarboxylic Acids. Design and Synthesis》 was published in Journal of Medicinal Chemistry. The article was written by Summa, Vincenzo; Petrocchi, Alessia; Matassa, Victor G.; Taliani, Marina; Laufer, Ralph; De Francesco, Raffaele; Altamura, Sergio; Pace, Paola. The article contains the following contents:

A new class of the HCV NS5b RNA-dependent RNA polymerase inhibitors, the dihyroxypyrimidinecarboxylic acid derivative, was designed from a diketoacid and meconic acid derivative discovered by screening. Mechanism of action and essential moieties required for activity were identified. The corresponding N-methylpyrimidinone was also prepared; both classes are novel, reversible, and selective inhibitors of the HCV NS5b polymerase with improved druglike characteristics. The results came from multiple reactions, including the reaction of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2COA of Formula: C11H8N2O4)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. COA of Formula: C11H8N2O4They 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.

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Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Formula: C5H6N2O3On September 8, 2022 ,《Fragment Ligands of the m6A-RNA Reader YTHDF2》 was published in ACS Medicinal Chemistry Letters. The article was written by Nai, Francesco; Nachawati, Raed; Zalesak, Frantisek; Wang, Xiang; Li, Yaozong; Caflisch, Amedeo. The article contains the following contents:

17 Small-mol. ligands that compete with N6-methyladenosine (m6A) for binding to the m6A-reader domain of YTHDF2 (YT521-B homol. domain family 2) was reported. Their binding mode at high resolution was determined by X-ray crystallog. and their affinity was quantified by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative had favorable ligand efficiencies of 0.47 and 0.38 kcal mol-1 per non-hydrogen atom, resp. They represent useful starting points for hit optimization. In addition to this study using 6-Methoxypyrimidine-2,4(1H,3H)-dione, there are many other studies that have used 6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6Formula: C5H6N2O3) was used in this study.

6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6) 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.Formula: C5H6N2O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia