Day: October 19, 2022

In 1977,Chemical & Pharmaceutical Bulletin included an article by Kato, Tetsuo; Oda, Noriichi; Ito, Isoo. Reference of 2-Methoxy-6-methylpyrimidin-4-amine. The article was titled 《Synthesis of compounds related to antitumor agents. VI. The conversion of 2,4-dialkoxypyrimidines into N-dialkyl-1,2,3,4-tetrahydro-2,4-dioxopyrimidines in the presence of p-toluenesulfonic acid derivatives》. The information in the text is summarized as follows:

Twelve 2,4-dialkoxypyrimidines I (R1 = Me, Et, Pr, allyl; R2 = Me, H; R3 = H, Br) were converted into 1,3-dialkyl-1,2,3,4-tetrahydro-2,4-dioxopyrimidines II by heating in the presence of p-MeC6H4SO3H or its derivatives, whereas III under similar conditions gave IV and V. In addition to this study using 2-Methoxy-6-methylpyrimidin-4-amine, there are many other studies that have used 2-Methoxy-6-methylpyrimidin-4-amine(cas: 51870-75-8Reference of 2-Methoxy-6-methylpyrimidin-4-amine) was used in this study.

2-Methoxy-6-methylpyrimidin-4-amine(cas: 51870-75-8) belongs to anime. Acylation is one of the most important reactions of primary and secondary amines; a hydrogen atom is replaced by an acyl group (a group derived from an acid, such as RCOOH or RSO3H, by removal of ―OH, such as RC(=O)―, RS(O)2―, and so on). Reagents may be acid chlorides (RCOC1, RSO2C1), anhydrides ((RCO)2O), or even esters (RCOOR′); the products are amides of the corresponding acids.Reference of 2-Methoxy-6-methylpyrimidin-4-amine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Journal of Physical Organic Chemistry included an article by Yuan, Hua; Li, Meng-Yang; Chen, Chun-Ni; Zhang, Yan; Liu, Wan-Qiang. Recommanded Product: 14001-69-5. The article was titled 《Substituent effects on the UV absorption energy of 2,5-disubstituted pyrimidines》. The information in the text is summarized as follows:

Pyrimidine-containing mols. have been extensively investigated in organic light emitting devices (OLEDs), solar cells, liquid crystals, and so on due to their perfect photoelec. properties. UV absorption is one of the interesting photoelec. properties. Systematical study of the substituent effects on the UV absorption energy of pyrimidine derivatives will guide to design functional mols. with specific photoelec. properties. In this paper, thirty-seven 2-X-5-Y pyrimidines with various substituents (X/Y=NH2, CH3, OCH3, NMe2, CF3, NO2, Cl, Br, I) were synthesized, and their UV spectra were recorded in anhydrous ethanol. The maximum absorption wavelength λmax(nm) were obtained and converted to wavenumber νmax(cm-1) (νmax = 1/λmax) for quant. structure-property relationship study. Hammett parameters (σ, σF, σR), electronegativity (χ), the excited-state substituent effect parameter (σCCex), and the heavy atom effect indicator (D) were employed as descriptors characterizing the mol. structure. By stepwise regression, a 5-descriptor linear regression model was built as νmax = 35 864.8122 + 6743.7901σR(X) + 8587.9937σR(Y) – 2042.7280Δσ2 + 1106.0034D(X) + 1451.8873χ(X) (R = 0.9861, S = 693.70, ARD = 1.49%, F = 218.68, Rcv = 0.9775, Scv = 881.25, ARDcv = 1.82%, n = 37). The model is proved of good stability and predictive performance by leave-one-out cross validation. Compared with the benzylideneaniline derivatives with CN bridge group, the substituent effects on the UV absorption energy of 2,5-disubstituted pyrimidines are quite different and much more complex. In the experiment, the researchers used 2-Methoxy-5-nitropyrimidine(cas: 14001-69-5Recommanded Product: 14001-69-5)

2-Methoxy-5-nitropyrimidine(cas: 14001-69-5) is a member of ether. Friedel Crafts reaction, for example, adds an alkyl or acyl group to aromatic ethers when they react with an alkyl or acyl halide in the presence of a Lewis acid as a catalyst.Recommanded Product: 14001-69-5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Marcelis, A. T. M.; Van der Plas, H. C. published an article on January 10 ,1986. The article was titled 《Ring transformations of heterocycles with nucleophiles. 33. Cycloadditions of 5-nitropyrimidines with ynamines. Formation of 3-nitropyridines, N-5-pyrimidyl-α-carbamoylnitrones, and 2,2a-dihydroazeto[2,3-d]-3,5-diazocines》, and you may find the article in Journal of Organic Chemistry.Formula: C6H7N3O4 The information in the text is summarized as follows:

The reaction of pyrimidines containing an electron-withdrawing substituent at C-5 with ynamines RCCR1 (I; R,R1 = Me, Et2N; Ph, Me2N; Ph, pyrrolidino) was studied. 5-(Ethoxycarbonyl)- and 5-(methylsulfonyl)pyridine undergo [4 + 2] cycloaddition to yield the substituted pyridines II and III resp. 5-Nitropyrimidines containing 2- and/or 4(6)-alkoxy or Me groups give a variety of products upon reaction with I. 4,6-Dimethoxy-5-nitropyrimidine undergoes [4 + 2] cycloaddition to give pyridine derivative IV (R2 = MeO) upon reaction with I (R = Me, R1 = Et2N) (V). Nitrone VI (R2 = MeO) is formed as main product upon reaction of V with 2,4-dimethoxy-5-nitropyrimidine. 5-Nitropyrimidines unsubstituted at C-4 and C-6 give dihydroazeto[2,3-d]diazocines upon reaction with 2 equiv of V. 4-Methoxy-5-nitropyrimidine yields pyridine IV and nitrone VI (R3 = H, R4 = MeO) upon reaction with V, and from 4-methyl-5-nitropyriidine, the pyridines IV (R2 = H, Me) dihydroazetodiazocine VII, and a nitrone are formed. Ynamine I (R = Ph; R1 = Me2N) is less reactive than V and does not react to form dihydroazetodiazocines with the 5-nitropyrimidines. Instead, nitrone VIII (R5 = H) and pyridine IX are formed upon reaction of I (R = Ph, R1 = Me2N) with 5-nitropyrimidine, and nitrone VIII (R5 = Ph) is formed with 2-phenyl-5-nitropyrimidine. In the experiment, the researchers used 2,4-Dimethoxy-5-nitropyrimidine(cas: 30561-07-0Formula: C6H7N3O4)

2,4-Dimethoxy-5-nitropyrimidine(cas: 30561-07-0) 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.Formula: C6H7N3O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Marcelis, A. T. M.; Van der Plas, H. C.; Harkema, S. published an article on January 25 ,1985. The article was titled 《Ring transformations of heterocycles with nucleophiles. 32. Cycloadditions of 5-nitropyrimidines with ynamines. Synthesis and crystal structure of a 2,2a-dihydroazeto[2,3-d]-3,5-diazocine, a novel heterocycle》, and you may find the article in Journal of Organic Chemistry.Synthetic Route of C5H5N3O3 The information in the text is summarized as follows:

5-Nitropyrimidine and its 2-Me, 2-Ph and 2-methoxy derivatives react with 1-(diethylamino)propyne to yield 2,2a-dihydroazeto[2,3-d]-3,5-diazocine 1-oxides I (R = H, Me, Ph, OMe). The crystal structure of N,N-diethyl-2,2a-dihydro-2,4,7-trimethyl-6-(diethylamino)azeto[2,3-d]-3,5-diazocine-2-carboxamide 1-oxide was determined The mechanism for the formation of this novel type of heterocycle is discussed. The experimental part of the paper was very detailed, including the reaction process of 2-Methoxy-5-nitropyrimidine(cas: 14001-69-5Synthetic Route of C5H5N3O3)

2-Methoxy-5-nitropyrimidine(cas: 14001-69-5) is a member of ether. Friedel Crafts reaction, for example, adds an alkyl or acyl group to aromatic ethers when they react with an alkyl or acyl halide in the presence of a Lewis acid as a catalyst.Synthetic Route of C5H5N3O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Norman, Mark H.; Zhu, Jiawang; Fotsch, Christopher; Bo, Yunxin; Chen, Ning; Chakrabarti, Partha; Doherty, Elizabeth M.; Gavva, Narender R.; Nishimura, Nobuko; Nixey, Thomas; Ognyanov, Vassil I.; Rzasa, Robert M.; Stec, Markian; Surapaneni, Sekhar; Tamir, Rami; Viswanadhan, Vellarkad N.; Treanor, James J. S. published an article in Journal of Medicinal Chemistry. The title of the article was 《Novel Vanilloid Receptor-1 Antagonists: 1. Conformationally Restricted Analogues of trans-Cinnamides》.Computed Properties of C11H6ClF3N2 The author mentioned the following in the article:

The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biol. evaluation of a series of conformationally constrained analogs of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74 (I), were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, resp.) and human TRPV1 (IC50 = 7.4 and 3.7 nM, resp.). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiol. response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund’s adjuvant in rats. The experimental part of the paper was very detailed, including the reaction process of 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6Computed Properties of C11H6ClF3N2)

4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6) 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. Computed Properties of C11H6ClF3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Inhibition of Lipid Signaling Enzyme Diacylglycerol Kinase ε Attenuates Mutant Huntingtin Toxicity》 were Zhang, Ningzhe; Li, Bensheng; Al-Ramahi, Ismael; Cong, Xin; Held, Jason M.; Kim, Eugene; Botas, Juan; Gibson, Bradford W.; Ellerby, Lisa M.. And the article was published in Journal of Biological Chemistry in 2012. Application of 213743-31-8 The author mentioned the following in the article:

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the protein huntingtin (Htt). Striatal and cortical neuronal loss are prominent features of this disease. No disease-modifying treatments have been discovered for HD. To identify new therapeutic targets in HD, we screened a kinase inhibitor library for mols. that block mutant Htt cellular toxicity in a mouse HD striatal cell model, Hdh111Q/111Q cells. We found that diacylglycerol kinase (DGK) inhibitor II (R59949) decreased caspase-3/7 activity after serum withdrawal in striatal Hdh111Q/111Q cells. In addition, R59949 decreased the accumulation of a 513-amino acid N-terminal Htt fragment processed by caspase-3 and blocked alterations in lipid metabolism during serum withdrawal. To identify the diacylglycerol kinase mediating this effect, we knocked down all four DGK isoforms expressed in the brain (β, γ, ε, and ζ) using siRNA. Only the knockdown of the family member, DGKε, blocked striatal Hdh111Q/111Q-mediated toxicity. We also investigated the significance of these findings in vivo. First, we found that reduced function of the Drosophila DGKε homolog significantly improves Htt-induced motor dysfunction in a fly model of HD. In addition, we find that the levels of DGKε are increased in the striatum of R6/2 HD transgenic mice when compared with littermate controls. Together, these findings indicate that increased levels of kinase DGKε contribute to HD pathogenesis and suggest that reducing its levels or activity is a potential therapy for HD. In the experiment, the researchers used 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Application of 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.Application of 213743-31-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Brakta, Mohamed; Daves, G. Doyle Jr. published their research in Journal of the Chemical Society on August 7 ,1992. The article was titled 《Efficient synthesis of 3H,5H-pyrrolo[3,2-d]pyrimidin-4-one》.Computed Properties of C5H4ClN3O3 The article contains the following contents:

Palladium-catalyzed cross-coupling of 4-iodo-6-methoxy-5-nitropyrmidine and trimethyl(tributylstannylethynyl)silane to form the corresponding 4-(trimethylsilylethynyl)pyrimidine I and subsequent construction of an annellated pyrrolo ring II provides an efficient route to the title pyrrolo[3,2-d]pyrimidine system III. In the experiment, the researchers used many compounds, for example, 4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5Computed Properties of C5H4ClN3O3)

4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5) 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 C5H4ClN3O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 1988,Saxena, Naveen K.; Hagenow, Brenda M.; Genzlinger, Gail; Turk, Steven R.; Drach, John C.; Townsend, Leroy B. published 《Synthesis and antiviral activity of certain 4-substituted and 2,4-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidines》.Journal of Medicinal Chemistry published the findings.Product Details of 90213-66-4 The information in the text is summarized as follows:

Alkylation of the Na salt of pyrimidine I (R = MeS, R1 = H) with AcOCH2CH2OCH2Br gave I (R = MeS, R1 = AcOCH2CH2OCH2) which was converted into the title pyrimidines II (R = MeS, R2 = Cl, NH2; R = H, OH, MeSO2, MeO, R2 = NH2). Similarly, I (R = Cl, NHAc, R1 = H) were alkylated and further transformed into II (R = Cl, R2 = Cl, NH2; R = NHAc, R2 = Cl; R = R2 = NH2). In tests of II involving human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), only slight activity and cytotoxicity were observed The most active compounds I(R = Cl, R1 = AcOCH2CH2OCH2) and II (R = R2 = Cl), were slightly more active against HCMV than acyclovir, but both compounds were inactive against HSV-1. The activity against HCMV, however, was not well separated from cytotoxicity leading to the conclusion that these compounds did not merit further study. In the experimental materials used by the author, we found 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 derivatives also play an important role in drug development, either in concert with other compounds or on their own. Product Details of 90213-66-4They 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

In 2017,Li, Wenlu; Sun, Qinsheng; Song, Lu; Gao, Chunmei; Liu, Feng; Chen, Yuzong; Jiang, Yuyang published 《Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings》.European Journal of Medicinal Chemistry published the findings.Name: 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of mols. simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-neg. breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 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.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Xie, Hui; Zeng, Shaogao; He, Yuwen; Zhang, Guicheng; Yu, Pengjiu; Zhong, Guifa; Xu, Hongjiang; Yang, Ling; Wang, Shanchun; Zhao, Xin; Hu, Wenhui published 《Rapid generation of a novel DPP-4 inhibitor with long-acting properties: SAR study and PK/PD evaluation》.European Journal of Medicinal Chemistry published the findings.Related Products of 90213-66-4 The information in the text is summarized as follows:

Drug compliance is critical for patients with chronic diseases such as diabetes. In our continuous effort to find better glucose-lowering agents, an exploration for long-acting DPP-4 inhibitors had been launched. Based on our previously reported compounds bearing a pyrrolopyrimidine scaffold, the lead compound 4a (IC50 = 2.3 nM, t1/2(rat) = 5.46 h) with pharmacokinetic superiority was rapidly determined Further SAR study indicated that the pyrrole ring was generally tolerable for variation, in which a β-substitution gave a better DPP-4 affinity. In depth evaluation of the pyrrole ring β position identified a highly potent compound 12a (IC50 = 0.76 nM, t1/2(rat) = 7.89 h). In vivo pharmacodynamics tests demonstrated similar or even slightly better sustained DPP-4 inhibition for compounds 4a and 12a compared with the first marketed once-weekly drug trelagliptin in this category, indicating that improvements to DPP-4 inhibitory activity or pharmacokinetic profile might be feasible ways to rapidly generate long-acting DPP-4 inhibitors. The experimental process involved the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4)

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. Related Products of 90213-66-4They 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