Day: October 19, 2022

In 2022,Vavaiya, Bhavinkumar; Patel, Shivani; Pansuriya, Vrajlal; Marvaniya, Vanita; Patel, Popatbhai published an article in Asian Journal of Chemistry. The title of the article was 《In silico and in vitro antitubercular studies for nitrogen rich hybrids of homopiperazine-pyrimidine-pyrazole adducts》.Computed Properties of C4H2Cl2N2 The author mentioned the following in the article:

Novel homopiperazine-pyrimidine-pyrazole hybrids (3a-j) were synthesized using Et 2-cyanoacetate and 4,6-dichloropyrimidine as starting materials by a multi-step process to afford Et 5-amino-1-(6-chloropyrimidin-4-yl)-1H-pyrazole-4-carboxylate in good yields using polar protic media. The intermediate 1, in two steps, chloroamine condensation followed by acid amine coupling, furnished the title compounds Et 5-amino-1-(6-(4-substituted aryl-1,4-diazepan-1-yl)pyrimidin-4-yl)-1H-pyrazole-4-carboxylate (3a-j). The synthesized compounds were docked in the crystal structure of Mycobacterium tuberculosis (PDB ID: 4TRO) to get insights into structural requirements for antitubercular activity. In vitro antitubercular activity against M. tuberculosis H37Rv strains showed that compounds 3a, 3d, 3e and 3g were found to be the most potent (Docking score: > -21; MIC = 1.6 μg/mL) among the synthesized mols. All the synthesized compounds showed acceptable drug-like properties which make them suitable for further lead modification using in silico design approaches. In the part of experimental materials, we found many familiar compounds, such as 4,6-Dichloropyrimidine(cas: 1193-21-1Computed Properties of C4H2Cl2N2)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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.Computed Properties of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Drewry, David H.; Annor-Gyamfi, Joel K.; Wells, Carrow I.; Pickett, Julie E.; Dederer, Verena; Preuss, Franziska; Mathea, Sebastian; Axtman, Alison D. published an article in Journal of Medicinal Chemistry. The title of the article was 《Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration》.Quality Control of 2,4-Dichloropyrimidine The author mentioned the following in the article:

The pyrimidine core has been utilized extensively to construct kinase inhibitors, including eight FDA-approved drugs. Because the pyrimidine hinge-binding motif is accommodated by many human kinases, kinome-wide selectivity of resultant mols. can be poor. This liability was seen as an advantage since it is well tolerated by many understudied kinases. We hypothesized that nonexemplified aminopyrimidines bearing side chains from well-annotated pyrimidine-based inhibitors with off-target activity on understudied kinases would provide us with useful inhibitors of these lesser studied kinases. Our strategy paired mixing and matching the side chains from the 2- and 4-positions of the parent compounds with modifications at the 5-position of the pyrimidine core, which is situated near the gatekeeper residue of the binding pocket. Utilizing this approach, we imparted improved kinome-wide selectivity to most members of the resultant library. Importantly, we also identified potent biochem. and cell-active lead compounds for understudied kinases like DRAK1, BMP2K, and MARK3/4. In the experiment, the researchers used many compounds, for example, 2,4-Dichloropyrimidine(cas: 3934-20-1Quality Control 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.Quality Control of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Bhuyan, Amar Jyoti; Bharali, Sourav Jyoti; Sharma, Abhilash; Dutta, Dhiraj; Gogoi, Pranjal; Saikia, Lakhinath published an article in Journal of Organic Chemistry. The title of the article was 《Copper-Catalyzed Direct Syntheses of Phenoxypyrimidines from Chloropyrimidines and Arylboronic Acids: A Cascade Avenue and Unconventional Substrate Pairs》.Reference of 4,6-Dichloropyrimidine The author mentioned the following in the article:

This synthetic methodol. for phenoxypyrimidines I (R = Ph, 2-methylphenyl, 3-nitrophenyl, etc.; R1 = H, Cl; X = N, CH;) and Et 4-[(4-hydroxyphenyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylate that avoids the direct use of phenols or their salts was described. In contrast to the general trend of delivering Suzuki-Miyaura cross-coupling products in reactions between aryl or alky halides and arylboronic acids, the substrate pairs used herein (chloropyrimidines and arylboronic acids RB(OH)2) led to C-O bond formation under the reaction conditions. In total, 25 phenoxypyrimidines I and Et 2-(methylthio)-4-phenoxypyrimidine-5-carboxylate, 6-(4-aminophenoxy)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione, 2-((6-methoxypyridin-3-yl)oxy)pyrimidine were successfully synthesized using the described protocol, 6 of which had a structural resemblance to etravirine such as N-methyl-N-(6-phenoxypyrimidin-4-yl)pyrimidin-2-amine. The results came from multiple reactions, including the reaction of 4,6-Dichloropyrimidine(cas: 1193-21-1Reference of 4,6-Dichloropyrimidine)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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 4,6-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 90213-66-4In 2019 ,《Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H3 receptor》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Frank, Annika; Meza-Arriagada, Francisco; Salas, Cristian O.; Espinosa-Bustos, Christian; Stark, Holger. The article conveys some information:

Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H3 receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, Ki value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4′-bipiperidin]-1′-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (Ki values of 7 nM and 6 nM, resp.) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H3 receptor ligands and yielded novel lead structures within the natural compound library against this target. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4SDS of cas: 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. SDS of cas: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Computed Properties of C4H2Cl2N2In 2020 ,《Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Xu, Yu; Hao, Shu-Yi; Zhang, Xiu-Juan; Li, Wen-Bo; Qiao, Xue-Peng; Wang, Zi-Xiao; Chen, Shi-Wu. The article conveys some information:

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a (I) showed moderate to high anti-proliferative activities against A549 (IC50 = 12.05 ± 0.45μM), HCT-116 (IC50 = 1.31 ± 0.41μM) and MCF-7 (IC50 = 20.53 ± 6.13μM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, resp. Furthermore, compound 12a induced apoptosis by upregulating the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the mol. docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Computed Properties of 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.Computed Properties of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Category: pyrimidinesIn 2017 ,《Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase》 appeared in Journal of Medicinal Chemistry. The author of the article were Brough, Paul A.; Baker, Lisa; Bedford, Simon; Brown, Kirsten; Chavda, Seema; Chell, Victoria; D’Alessandro, Jalanie; Davies, Nicholas G. M.; Davis, Ben; Le Strat, Loic; Macias, Alba T.; Maddox, Daniel; Mahon, Patrick C.; Massey, Andrew J.; Matassova, Natalia; McKenna, Sean; Moore, Jonathan D.; Murray, James B.; Northfield, Christopher J.; Parry, Charles; Parsons, Rachel; Roughley, Stephen D.; Shaw, Terry; Simmonite, Heather; Stokes, Stephen; Surgenor, Allan; Stefaniak, Emma; Robertson, Alan; Wang, Yikang; Webb, Paul; Whitehead, Neil; Wood, Mike. The article conveys some information:

Libraries of non-purified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro. In the experimental materials used by the author, we found 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

《Study on the preparation of heteroaryl substituted enamines. A simple synthesis of heteroaryl substituted acetaldoximes from enamines》 was written by Copar, Anton; Stanovnik, Branko; Tisler, Miha. Safety of 2-Methoxy-4-methylpyrimidine And the article was included in Journal of Heterocyclic Chemistry on April 30 ,1996. The article conveys some information:

A comparative study of the reactivity of Me groups towards N,N-dimethylformamide di-Me acetal and tert-butoxybis(dimethylamino)methane was carried out on Me substituted six-membered nitrogen containing heterocycles to give enamines, which were easily transformed to oximes by treating with hydroxylamine hydrochloride in methanol. Most of them were isolated as (E,Z)-oximes of heteroarylacetaldehyde, but 5-(1,2,4-triazinyl) substituted derivatives were isolated as (E,Z)-oximes of 2,5-dihydro-1,2,4-triazin-(Z)-5-ylideneacetaldehyde. Oximes were finally transformed to the corresponding acetontriles and 3-(dimethylamino)acrylonitriles. In the experimental materials used by the author, we found 2-Methoxy-4-methylpyrimidine(cas: 14001-60-6Safety of 2-Methoxy-4-methylpyrimidine)

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.Safety of 2-Methoxy-4-methylpyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of C17H16N2O5On May 31, 2002, Kumamoto, Hiroki; Tanaka, Hiromichi published an article in Journal of Organic Chemistry. The article was 《Simple Entry to 3′-Substituted Analogues of Anti-HIV Agent Stavudine Based on an Anionic O → C Stannyl Migration》. The article mentions the following:

Reaction of 5′-O-protected derivatives of the anti-HIV agent stavudine (d4T) with LTMP was investigated with the aim to lithiate the vinylic hydrogens (H-3′ and H-2′). When the lithiation of the 5′-O-tert-butyldiphenylsilyl derivative I was carried out in the presence of HMPA, an anionic silyl migration took place to give the 3′-C-silylated product II. The stannyl version of this reaction was found to be also possible, which has disclosed a highly simple entry to the d4T analogs variously substituted at the 3′-position by manipulating the 3′-C-stannyl d4T as a common intermediate. In the experiment, the researchers used many compounds, for example, ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Electric Literature of C17H16N2O5)

((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.Electric Literature of C17H16N2O5

Referemce:
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

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.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia