Month: October 2022

In 2022,Boffey, Helen K.; Rooney, Timothy P. C.; Willems, Henriette M. G.; Edwards, Simon; Green, Christopher; Howard, Tina; Ogg, Derek; Romero, Tamara; Scott, Duncan E.; Winpenny, David; Duce, James; Skidmore, John; Clarke, Jonathan H.; Andrews, Stephen P. published an article in Journal of Medicinal Chemistry. The title of the article was 《Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode》.HPLC of Formula: 90213-66-4 The author mentioned the following in the article:

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunol. disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochem. properties of the selective PI5P4Kγ inhibitor, NIH-12848 (1). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kβ. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chem. series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4HPLC of Formula: 90213-66-4) 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. HPLC of Formula: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 3764-01-0In 2016 ,《Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials》 appeared in Journal of Medicinal Chemistry. The author of the article were Norcross, Neil R.; Baragana, Beatriz; Wilson, Caroline; Hallyburton, Irene; Osuna-Cabello, Maria; Norval, Suzanne; Riley, Jennifer; Stojanovski, Laste; Simeons, Frederick R. C.; Porzelle, Achim; Grimaldi, Raffaella; Wittlin, Sergio; Duffy, Sandra; Avery, Vicky M.; Meister, Stephan; Sanz, Laura; Jimenez-Diaz, Belen; Angulo-Barturen, Inigo; Ferrer, Santiago; Martinez, Maria Santos; Gamo, Francisco Javier; Frearson, Julie A.; Gray, David W.; Fairlamb, Alan H.; Winzeler, Elizabeth A.; Waterson, David; Campbell, Simon F.; Willis, Paul; Read, Kevin D.; Gilbert, Ian H.. The article conveys some information:

In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound I showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P 450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead mol. with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting.2,4,6-Trichloropyrimidine(cas: 3764-01-0Related Products of 3764-01-0) was used in this study.

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.Related Products of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Recommanded Product: 3934-20-1In 2021 ,《Discovery of ASTX029, A Clinical Candidate Which Modulates the Phosphorylation and Catalytic Activity of ERK1/2》 was published in Journal of Medicinal Chemistry. The article was written by Heightman, Tom D.; Berdini, Valerio; Bevan, Luke; Buck, Ildiko M.; Carr, Maria G.; Courtin, Aurelie; Coyle, Joseph E.; Day, James E. H.; East, Charlotte; Fazal, Lynsey; Griffiths-Jones, Charlotte M.; Howard, Steven; Kucia-Tran, Justyna; Martins, Vanessa; Muench, Sandra; Munck, Joanne M.; Norton, David; O’Reilly, Marc; Palmer, Nicholas; Pathuri, Puja; Peakman, Torren M.; Reader, Michael; Rees, David C.; Rich, Sharna J.; Shah, Alpesh; Wallis, Nicola G.; Walton, Hugh; Wilsher, Nicola E.; Woolford, Alison J.-A.; Cooke, Michael; Cousin, David; Onions, Stuart; Shannon, Jonathan; Watts, John; Murray, Christopher W.. The article contains the following contents:

Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are positioned at a key node in this pathway, making them important targets for therapeutic intervention. Recently, a number of ERK1/2 inhibitors have been advanced to investigational clin. trials in patients with activating mutations in B-Raf proto-oncogene or Ras. Here, we describe the discovery of the clin. candidate ASTX029 (15)(I) through structure-guided optimization of our previously published isoindolinone lead (7). The medicinal chem. campaign focused on addressing CYP3A4-mediated metabolism and maintaining favorable physicochem. properties. These efforts led to the identification of ASTX029, which showed the desired pharmacol. profile combining ERK1/2 inhibition with suppression of phospho-ERK1/2 (pERK) levels, and in addition, it possesses suitable preclin. pharmacokinetic properties predictive of once daily dosing in humans. ASTX029 is currently in a phase I-II clin. trial in patients with advanced solid tumors. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Recommanded Product: 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.Recommanded Product: 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Tuning nuclear receptor selectivity of Wy14,643 towards selective retinoid X receptor modulation》 was written by Pollinger, Julius; Gellrich, Leonie; Schierle, Simone; Kilu, Whitney; Schmidt, Jurema; Kalinowsky, Lena; Ohrndorf, Julia; Kaiser, Astrid; Heering, Jan; Proschak, Ewgenij; Merk, Daniel. Electric Literature of C4HCl3N2This research focused onWy14643 retinoid x receptor pharmacokinetics. The article conveys some information:

The fatty acid sensing nuclear receptor families retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs) hold therapeutic potential in neurodegeneration. Valuable pleiotropic activities of Wy14,643 (I) in models of such conditions exceed its known PPAR agonistic profile. Here, we characterize the compound as an RXR agonist explaining the pleiotropic effects and report its systematic structure-activity relationship anal. with the discovery of specific mol. determinants driving activity on PPARs and RXRs. We have designed close analogs of the drug comprising selective and dual agonism on RXRs and PPARs that may serve as superior pharmacol. tools to study the role and interplay of the nuclear receptors in various pathologies. A systematically optimized high potency RXR agonist (II) revealed activity in vivo and active concentrations in brain. With its lack of RXR/liver X receptor-mediated side effects and superior profile compared to classical rexinoids, it establishes a new class of innovative RXR modulators to overcome key challenges in RXR targeting drug discovery. The results came from multiple reactions, including the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Electric Literature of C4HCl3N2)

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.Electric Literature of C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 519032-07-6On November 16, 2006 ,《4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species》 appeared in Journal of Medicinal Chemistry. The author of the article were Summa, Vincenzo; Petrocchi, Alessia; Matassa, Victor G.; Gardelli, Cristina; Muraglia, Ester; Rowley, Michael; Paz, Odalys Gonzalez; Laufer, Ralph; Monteagudo, Edith; Pace, Paola. The article conveys some information:

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochem. properties, pharmacokinetic profiles, and potency led to the identification of (I) in the dihydroxypyrimidine series and (II) in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclin. species. After reading the article, we found that the author used Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6SDS of cas: 519032-07-6)

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. SDS of cas: 519032-07-6They 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 1966,Journal of Organic Chemistry included an article by Temple, Carroll Jr.; Montgomery, John A.. Formula: C6H7Cl2N3. The article was titled 《Some unusual reactions of 6-chloropurines with thioureas. 6-Alkylthiopurines and 2,2-diamino-2H-thiazolo[3,4,5-gh]purines from 2-(purin-6-yl)-2-thiopseudoureas》. The information in the text is summarized as follows:

Reaction of 6-chloropurine (I) with thiourea gave, in addition to purine-6(1H)-thione (II), 2,2-diamino-2H-thiazolo[3,4,5-gh]purine (III). 1-Ethyl-2-thiourea and I provided the corresponding ethyl derivative of III. From the reaction of 6-chloro-2-ethylpurine and thiourea in PrOH, 2-ethylpurine-6(1 H)-thione, 2,2-diamino-7-ethyl-2H-thiazolo[3,4,5-gh]purine, and 2-ethyl-6-(propylthio)purine (IV) were obtained, the formation of IV resulting from solvent participation. 6-Chloro-2,9-diethylpurine and thiourea in PrOH gave 2,9-diethyl-2-(propylthio)purine as a major component. Treatment of I, 2,6-dichloropurine, and 2-amino-6-chloropurine with 2-imidazolidinethione gave the corresponding 6-(2-imidazolinylthio)purine hydrochlorides (V, VI, and VII), resp. The free base of V and VI but not of VII appeared to form derivatives of III by intramol. addition Basic hydrolysis converted V to II, VI to 2-chlorohypoxanthine, and VII to thioguanine containing a trace of guanine. The results came from multiple reactions, including the reaction of 4,6-Dichloro-2-ethylpyrimidin-5-amine(cas: 6237-96-3Formula: C6H7Cl2N3)

4,6-Dichloro-2-ethylpyrimidin-5-amine(cas: 6237-96-3) belongs to anime. Nitrous acid converts secondary amines (aliphatic or aromatic) to N-nitroso compounds (nitrosamines): R2NH + HNO2 → R2N―NO. Some nitrosamines are potent cancer-inducing substances, and their possible formation is a serious consideration when nitrites, which are salts of nitrous acid, are present in foods or pharmaceutical preparations. Tertiary amines give rise to nitrosamines more slowly; an alkyl group is eliminated as an aldehyde or ketone, along with nitrous oxide, N2O.Formula: C6H7Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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