Day: October 20, 2022

The author of 《Designing a chemical inhibitor for the AAA protein spastin using active site mutations》 were Cupido, Tommaso; Pisa, Rudolf; Kelley, Megan E.; Kapoor, Tarun M.. And the article was published in Nature Chemical Biology in 2019. Category: pyrimidines The author mentioned the following in the article:

Spastin is a microtubule-severing AAA (ATPases associated with diverse cellular activities) protein needed for cell division and intracellular vesicle transport. Currently, we lack chem. inhibitors to probe spastin function in such dynamic cellular processes. To design a chem. inhibitor of spastin, we tested selected heterocyclic scaffolds against wild-type protein and constructs with engineered mutations in the nucleotide-binding site that do not substantially disrupt ATPase activity. These data, along with computational docking, guided improvements in compound potency and selectivity and led to spastazoline, a pyrazolyl-pyrrolopyrimidine-based cell-permeable probe for spastin. These studies also identified spastazoline-resistance-conferring point mutations in spastin. Spastazoline, along with the matched inhibitor-sensitive and inhibitor-resistant cell lines we generated, were used in parallel experiments to dissect spastin-specific phenotypes in dividing cells. Together, our findings suggest how chem. probes for AAA proteins, along with inhibitor resistance-conferring mutations, can be designed and used to dissect dynamic cellular processes. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Category: pyrimidines)

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. Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yuan, Kai; Ji, Minghui; Xie, Shengnan; Qiu, Zhixia; Chen, Weijiao; Min, Wenjian; Xia, Fei; Zheng, Mingming; Wang, Xiao; Li, Jiaxing; Hou, Yi; Kuang, Wenbin; Wang, Liping; Gu, Wanjian; Li, Zhiyu; Yang, Peng published an article in 2022. The article was titled 《Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia》, and you may find the article in Journal of Medicinal Chemistry.Category: pyrimidines The information in the text is summarized as follows:

Nowadays, the simultaneous inhibition of two or more pathways plays an increasingly important role in cancer treatment due to the complex and diverse pathogenesis of cancer, and the combination of the cyclin-dependent kinase 6 (CDK6) inhibitor and PIM1 inhibitor was found to generate synergistic effects in acute myeloid leukemia (AML) treatment. Therefore, we discovered a novel lead 1 targeting CDK6/PIM1 via pharmacophore-based and structure-based virtual screening, synthesized five different series of new derivates, and obtained a potent and balanced dual CDK6/PIM1 inhibitor 51 (I), which showed high kinase selectivity. Meanwhile, 51 displayed an excellent safety profile and great pharmacokinetic properties. Furthermore, 51 displayed stronger potency in reducing the burden of AML than palbociclib and SMI-4a in vivo. In summary, we offered a new direction for AML treatment and provided a great lead compound for AML preclin. studies. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Category: pyrimidines)

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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Dannheim, Friederike M.; Walsh, Stephen J.; Orozco, Carolina T.; Hansen, Anders Hoejgaard; Bargh, Jonathan D.; Jackson, Sophie E.; Bond, Nicholas J.; Parker, Jeremy S.; Carroll, Jason S.; Spring, David R. published an article in Chemical Science. The title of the article was 《All-in-one disulfide bridging enables the generation of antibody conjugates with modular cargo loading》.Product Details of 3764-01-0 The author mentioned the following in the article:

Antibody-drug conjugates (ADCs) are valuable therapeutic entities which leverage the specificity of antibodies to selectively deliver cytotoxins to antigen-expressing targets such as cancer cells. However, current methods for their construction still suffer from a number of shortcomings. For instance, using a single modification technol. to modulate the drug-to-antibody ratio (DAR) in integer increments while maintaining homogeneity and stability remains exceptionally challenging. Herein, we report a novel method for the generation of antibody conjugates with modular cargo loading from native antibodies. Our approach relies on a new class of disulfide rebridging linkers, which can react with eight cysteine residues, thereby effecting all-in-one bridging of all four interchain disulfides in an IgG1 antibody with a single linker mol. Modification of the antibody with the linker in a 1 : 1 ratio enabled the modulation of cargo loading in a quick and selective manner through derivatization of the linker with varying numbers of payload attachment handles to allow for attachment of either 1, 2, 3 or 4 payloads (fluorescent dyes or cytotoxins). Assessment of the biol. activity of these conjugates demonstrated their exceptional stability in human plasma and utility for cell-selective cytotoxin delivery or imaging/diagnostic applications. 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. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Product Details of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 3934-20-1In 2020 ,《Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors》 appeared in Bioorganic Chemistry. The author of the article were Vettorazzi, Marcela; Insuasty, Daniel; Lima, Santiago; Gutierrez, Lucas; Nogueras, Manuel; Marchal, Antonio; Abonia, Rodrigo; Andujar, Sebastian; Spiegel, Sarah; Cobo, Justo; Enriz, Ricardo D.. The article conveys some information:

Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurol. and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a great interest in the development new SphK1 inhibitors as a potential new treatment for cancer. In a search for new SphK1 inhibitors we selected the well-known SKI-II inhibitor as the starting structure and we synthesized a new inhibitor structurally related to SKI-II with a significant but moderate inhibitory effect. In a second approach, based on our mol. modeling results, we designed new structures based on the structure of PF-543, the most potent known SphK1 inhibitor. Using this approach, we report the design, synthesis and biol. evaluation of a new series of compounds with inhibitory activity against both SphK1 and SphK2. These new inhibitors were obtained incorporating new connecting chains between their polar heads and hydrophobic tails. On the other hand, the combined techniques of mol. dynamics simulations and QTAIM calculations provided complete and detailed information about the mol. interactions that stabilize the different complexes of these new inhibitors with the active sites of the SphK1. This information will be useful in the design of new SphK inhibitors. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Application of 3934-20-1)

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 of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Pyridopyrimidinone derivatives as potent and selective c-Jun N-terminal kinase (JNK) inhibitors》 was written by Zheng, Ke; Park, Chul Min; Iqbal, Sarah; Hernandez, Pamela; Park, HaJeung; LoGrasso, Philip V.; Feng, Yangbo. Computed Properties of C6H7N3O2S And the article was included in ACS Medicinal Chemistry Letters on April 9 ,2015. The article conveys some information:

A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure-activity relationships (SARs) were systematically developed utilizing biochem. and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. (trans)-1-Isopropyl-3-[4-(8-isopropyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl-amino)-cyclohexyl]urea (I), was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 μM), had high potency in functional cell based assays, and had high stability in human liver microsome (t1/2 = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of (I) and (trans)-1-[4-(8-Cyclopentyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-cyclohexyl]-3-isopropyl-urea in JNK3 were solved at 2.0 Å. These structures elucidated the binding mode (Type-I binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition. The results came from multiple reactions, including the reaction of 4-Amino-2-(methylthio)pyrimidine-5-carboxylic acid(cas: 771-81-3Computed Properties of C6H7N3O2S)

4-Amino-2-(methylthio)pyrimidine-5-carboxylic acid(cas: 771-81-3) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).Computed Properties of C6H7N3O2S

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2010,Tumkevicius, Sigitas; Dodonova, Jelena; Kazlauskas, Karolis; Masevicius, Viktoras; Skardziute, Lina; Jursenas, Saulius published 《Synthesis and photophysical properties of oligoarylenes with a pyrrolo[2,3-d]pyrimidine core》.Tetrahedron Letters published the findings.Recommanded Product: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The information in the text is summarized as follows:

The Pd-catalyzed Suzuki-Miyaura reaction of 2,4-dichloropyrrolo[2,3-d]pyrimidine with arylboronates was studied. Pd(OAc)2/dicyclohexyl(2-biphenyl)phosphine/K3PO4 was an efficient catalyst system to prepare 4-aryl-2-chloro- and 2,4-diarylpyrrolo[2,3-d]pyrimidines. Novel non-linear mols. consisting of a pyrrolo[2,3-d]pyrimidine core and aryl branches were elucidated as blue light-emitters with fluorescence quantum yields of 4-67% in THF solution The impact of an electron-withdrawing CO2CMe3 group attached to the pyrrole ring of pyrrolopyrimidines on optical properties is discussed. In addition to this study using 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine, there are many other studies that have used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Recommanded Product: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine) 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. Recommanded Product: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2014,Su, Qibin; Ioannidis, Stephanos; Chuaqui, Claudio; Almeida, Lynsie; Alimzhanov, Marat; Bebernitz, Geraldine; Bell, Kirsten; Block, Michael; Howard, Tina; Huang, Shan; Huszar, Dennis; Read, Jon A.; Rivard Costa, Caroline; Shi, Jie; Su, Mei; Ye, Minwei; Zinda, Michael published 《Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors》.Journal of Medicinal Chemistry published the findings.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:

Structure based design, synthesis, and biol. evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clin. candidate AZD1480 (I), optimization of the series led to the discovery of compound II, a potent, orally bioavailable Jak2 inhibitor. Compound II displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound II demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range. In the experimental materials used by the author, we found 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. 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. Synthetic Route of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Kamijo, Shin; Kamijo, Kaori; Murafuji, Toshihiro published 《Synthesis of Alkylated Pyrimidines via Photoinduced Coupling Using Benzophenone as a Mediator》.Journal of Organic Chemistry published the findings.Formula: C4HCl3N2 The information in the text is summarized as follows:

Alkylated pyrimidines such as I (R = Cl, MeO) were prepared regioselectively by photochem. coupling of cyclic ethers, carbamates, γ-butyrolactam, and tetrahydrothiophene (THT) with methanesulfonylpyrimidines such as II (R = Cl, MeO) using benzophenone as the sole photochem. mediator. The heterocyclic substituents were selectively introduced at the nonacidic C(sp3)-H bond proximal to their heteroatoms, and at the methanesulfonyl-substituted position of the pyrimidines. This method was used to prepare an analog of the Aurora kinase inhibitor MK-0457. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Formula: C4HCl3N2)

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.Formula: C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Andrs, Martin; Pospisilova, Monika; Seifrtova, Martina; Havelek, Radim; Tichy, Ales; Vejrychova, Katerina; Polednikova, Michaela; Gorecki, Lukas; Jun, Daniel; Korabecny, Jan; Rezacova, Martina published 《Purin-6-one and pyrrolo[2,3-d]pyrimidin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity》.Future Medicinal Chemistry published the findings.Category: pyrimidines The information in the text is summarized as follows:

Aim: DNA damage response plays an eminent role in patients′ response to conventional chemotherapy and radiotherapy. Its inhibition is of great interest as it can overcome cancer cell resistance and reduce the EDs of DNA damaging agents. Results & methodol.: We have focused our research on phosphatidylinositol 3-kinase-related kinases and prepared 35 novel compounds through a scaffold hopping approach. The newly synthesized inhibitors were tested on a panel of nine cancer and one healthy cell lines alone and in combination with appropriate doses of doxorubicin. Conclusion: Five novel compounds 4f, 10b, 15g, 7e and 15f in combination with doxorubicin showed significant antiproliferative effect on seven cancer cell lines while not affecting the cell growth alone. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Category: pyrimidines)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Category: pyrimidinesThey 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

AlNeyadi, Shaikha S.; Adem, Abdu; Amer, Naheed; Ghattas, Mohammad A.; Atatreh, Noor; Salem, Alaa A.; Abdou, Ibrahim M. published their research in Results in Chemistry in 2021. The article was titled 《Activation of the GLP-1 receptor by chloropyrimidine derivatives》.COA of Formula: C4H2Cl2N2 The article contains the following contents:

The anti-diabetic activities of a series of chloropyrimidine derviativeswere investigated after they were designed, synthesized, and docked against the GLP-1 receptor target. In comparison to exenatide, which was utilized as a reference drug, the three chloropyrimidine synthesized compounds I, II and III exhibited potent in vitro and in vivo antidiabetic activities. Interestingly, compounds I, II and III showed to be the most effective in lowering blood glucose levels and led to even higher glucose uptake than the reference drug, exenatide. Consistent with the in vitro and in vivo data, compounds II and III had the lowest docking energy scores (Glide-XP score = 5.1 kcal/mol) and the greatest ligand efficiency score (> – 0.40 kcal/mol) among all docked compounds These findings give up new possibilities for the development of high-efficacy compounds to treat hyperglycemia. The experimental process involved the reaction of 4,6-Dichloropyrimidine(cas: 1193-21-1COA of Formula: C4H2Cl2N2)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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.COA of Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia