Day: January 5, 2023

Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3 was written by Disch, Jeremy S.;Evindar, Ghotas;Chiu, Cynthia H.;Blum, Charles A.;Dai, Han;Jin, Lei;Schuman, Eli;Lind, Kenneth E.;Belyanskaya, Svetlana L.;Deng, Jianghe;Coppo, Frank;Aquilani, Leah;Graybill, Todd L.;Cuozzo, John W.;Lavu, Siva;Mao, Cheney;Vlasuk, George P.;Perni, Robert B.. And the article was included in Journal of Medicinal Chemistry in 2013.Product Details of 175137-21-0 This article mentions the following:

The sirtuins SIRT1, SIRT2, and SIRT3 are NAD⁺ dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncol., and neurodegenerative disorders. Encoded library technol. (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small mols., which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency. Subsequent SAR studies to improve physiochem. properties identified the potent drug like analogs 4-(4-(2-Pivalamidoethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide and 4-(4-(2-(Methylsulfonamido)ethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide. Crystallog. studies of N²-(2-(1-(6-Carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl)ethyl)-N⁵-ethylthiophene-2,5-dicarboxamide, 4-(4-(2-Pivalamidoethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide, and 4-(4-(2-(Methylsulfonamido)ethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research. In the experiment, the researchers used many compounds, for example, 4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0Product Details of 175137-21-0).

4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. Pyrimidine derivatives 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.Product Details of 175137-21-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

9H-Pyrimido[4,5-b]indole-2,4-diones. The acid-catalyzed cyclization of 6-(phenylhydrazino)uracils was written by Wright, G. E.. And the article was included in Journal of Heterocyclic Chemistry in 1976.Formula: C6H9N3OS This article mentions the following:

The 6-(phenylhydrazino)uracils under facile Fischer-type cyclization in both N HCl and in HCO2H at reflux to give 9H-pyrimido[4,5-b]indol-2,4-diones, e.g., I. Yields are related to substituent effects and side reactions. In the reaction of 6-(phenylhydrazino)uracil itself with HCl, the major competing reaction is hydrolysis to barbituric acid and PhNHNH2, whereas in HCO2H 1-phenyl-3-carboxamidomethyl-1,2,4-triazole is obtained. NMR spectra of pyrimido[4,5-b]indole-2,4-diones provide examples of peri effects on H chem. shifts. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Formula: C6H9N3OS).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Formula: C6H9N3OS

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis with pyrimidinyllithium compounds and properties of a series of 4,4′- and 4,5′-bipyrimidine derivatives was written by Strekowski, Lucjan. And the article was included in Seria Chemia (Uniwersytet im. Adama Mickiewicza w Poznaniu) in 1976.Name: 5-Bromo-2-chloro-4-(methylthio)pyrimidine This article mentions the following:

4,5′-Bipyrimidines with methoxy or methylthio substituents at positions 4′ and 6 were prepared In a typical run, a 5-bromo-4-methoxypyrimidine was treated with ∼0.6-0.8 molar equivalent BuLi, kept, then quenched with H2O. 5-Bromo-2,4-bis(alkylthio)pyrimidines and 5-bromo-2,4-di-tert-butoxypyrimidine (I) in THF gave rise to mixtures of 4,4′- and 4,5′-bipyrimidine, but in Et2O I gave rise to the 4,5′-bipyrimidine only. The bipyrimidines can be formed through the nucleophilic addition of pyrimidinyl-lithiums to 4,5-didehydropyrimidines or to the N(1)-C(6) azomethine bond in the pyrimidine ring of the substrates. 5-Bromo-2,4-dichloropyrimidine on treatment with controlled quantities of nucleophiles, such as alkoxide and alkylmercaptide anions and secondary amines, could exchange its Cl at position 4 with high selectivity. A nucleophilic displacement of the Cl at position 2 in the products gave rise to 5-bromopyrimidines with various substituents at positions 2 and 4. Mass spectra of the pyrimidine derivatives were reported. Some of the compounds showed unusual decomposition patterns of the mol. ions. In the experiment, the researchers used many compounds, for example, 5-Bromo-2-chloro-4-(methylthio)pyrimidine (cas: 59549-51-8Name: 5-Bromo-2-chloro-4-(methylthio)pyrimidine).

5-Bromo-2-chloro-4-(methylthio)pyrimidine (cas: 59549-51-8) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Name: 5-Bromo-2-chloro-4-(methylthio)pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis, structures, electrochemical studies and antioxidant activity of 5-aryl-4-oxo-3,4,5,8-tetrahydropyrido[2,3-d]pyrimidine-7-carboxylic acids was written by Quiroga, Jairo;Romo, Pablo E.;Ortiz, Alejandro;Isaza, Jose Hipolito;Insuasty, Braulio;Abonia, Rodrigo;Nogueras, Manuel;Cobo, Justo. And the article was included in Journal of Molecular Structure in 2016.Application In Synthesis of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one This article mentions the following:

The synthesis of 5-aryl-4-oxo-3,4,5,8-tetrahydropyrido[2,3-d]pyrimidine-7-carboxylic acids I (X = SCH₃, OCH₃; R² = 4-Cl, 3,4-OCH₂O, 4-CH₃, etc.) from the reaction of 6-aminopyrimidines with arylidene derivatives of pyruvic acid under microwave and ultrasound irradiation is described. The orientation of cyclization process was determined by NMR measurements. The methodol. provides advantages such as high yields, environmentally friendly and no use of solvents. The antioxidant properties, DPPH free radical scavenging, ORAC, and anodic potential oxidation of the new pyridopyrimidines were studied. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Application In Synthesis of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Application In Synthesis of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Antibiotics in elderly Chinese population and their relations with hypertension and pulse pressure was written by Li, Zhenkun;Liu, Kaiyong;Zhao, Jianing;Yang, Linsheng;Chen, Guimei;Liu, Annuo;Wang, Qunan;Wang, Sufang;Li, Xiude;Cao, Hongjuan;Tao, Fangbiao;Zhang, Dongmei. And the article was included in Environmental Science and Pollution Research in 2022.Electric Literature of C11H12N4O3S This article mentions the following:

Although antibiotic exposure in the general population has been well documented by a biomonitoring approach, epidemiol. data on the relationships between urinary antibiotic burden in the elderly with blood pressure (BP) are still lacking. The current study revealed thirty-four antibiotics in urine specimens from 990 elderly patients in Lu’an City, China, with detection frequencies ranging from 0.2 to 35.5%. Among the elderly, the prevalence of hypertension was 72.0%, and 12 antibiotics were detected in more than 10% of individuals with hypertension. The elderly with hypertension had the maximum daily exposure (5450.45μg/kg/day) to fluoroquinolones (FQs). Multiple linear regression analyses revealed significant associations of BP and pulse pressure (PP) with exposure to specific antibiotics. The estimated β values (95% confidence interval) of associations with systolic blood pressure (SBP) in the right arm were 4.42 (1.15, 7.69) for FQs, 4.26 (0.52, 8.01) for the preferred as human antibiotics (PHAs), and 3.48 (0.20, 6.77) for the mixtures (FQs + tetracyclines [TCs] (tertile 3 vs. tertile 1)), resp. Increased concentrations of TCs were associated with decreased diastolic BP (DBP; tertile 3: -1.75 [-3.39, -0.12]) for the right arm. Higher levels of FQs (tertile 3: 4.28 [1.02, 7.54]), PHAs (tertile 3: 4.25 [0.49, 8.01]), and FQs + TCs (tertile 3: 3.99 [0.71, 7.26]) were associated with increased SBP, and an increase in DBP for FQs (tertile 3: 1.82 [0.22, 3.42]) was shown in the left arm. Also, higher urinary concentrations of FQs (tertile 3: 3.18 [0.53, 5.82]), PHAs (tertile 3: 3.42 [0.40, 6.45]), and FQs + TCs (tertile 3: 3.06 [0.40, 5.72]) were related to increased PP, whereas a decline in PP for TCs (tertile 2: -2.93 [-5.60, -0.25]) in the right arm. And increased concentrations of penicillin V (tertile 3: 5.31 [1.53, 9.10]) and FQs + TCs (tertile 3: 2.84 [0.19, 5.49]) were related to higher PP in the left arm. By utilizing restricted cubic splines, our current study revealed a potential nonlinear dose-response association between FQ exposure and hypertension risk. In conclusion, this investigation is the first to present antibiotic exposure using a biomonitoring approach, and informs understanding of impacts of antibiotic residues, as emerging hazardous pollutants, on the hypertension risk in the elderly. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Electric Literature of C11H12N4O3S).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Pyrimidine derivatives 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.Electric Literature of C11H12N4O3S

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Diastereoselective Trifluoroacetylation of Highly Substituted Pyrrolidines by a Dakin-West Process was written by Baumann, Marcus;Baxendale, Ian R.. And the article was included in Journal of Organic Chemistry in 2016.Safety of 2-Methoxypyrimidine-5-carbaldehyde This article mentions the following:

A robust approach allowing for the efficient trifluoroacetylation of a series of highly substituted pyrrolidines in a diastereoselective manner is reported. The transformation is based on a Dakin-West reaction of advanced pyrrolidine 2-carboxylic acid derivatives that can be assembled stereoselectively in four synthetic steps. Importantly, this work demonstrates how the introduction of lateral substituents on the pyrrolidine scaffold enables the generation of the desired trifluoroacetylation products, which was not possible previously due to the exclusive formation of trifluoromethylated oxazoles. In the course of this work we succeeded for the first time in isolating and characterizing (HRMS, IR, ¹H, ¹³C and ¹⁹F NMR, X-ray) different intermediates of the Dakin-West reaction allowing us to probe its mechanism. In the experiment, the researchers used many compounds, for example, 2-Methoxypyrimidine-5-carbaldehyde (cas: 90905-32-1Safety of 2-Methoxypyrimidine-5-carbaldehyde).

2-Methoxypyrimidine-5-carbaldehyde (cas: 90905-32-1) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Safety of 2-Methoxypyrimidine-5-carbaldehyde

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Discovery of the c-Jun N-Terminal Kinase Inhibitor CC-90001 was written by Nagy, Mark A.;Hilgraf, Robert;Mortensen, Deborah S.;Elsner, Jan;Norris, Stephen;Tikhe, Jayashree;Yoon, Won;Paisner, David;Delgado, Mercedes;Erdman, Paul;Haelewyn, Jason;Khambatta, Godrej;Xu, Li;Romanow, William J.;Condroski, Kevin;Bahmanyar, Sogole;McCarrick, Meg;Benish, Brent;Blease, Kate;LeBrun, Laurie;Moghaddam, Mehran F.;Apuy, Julius;Canan, Stacie S.;Bennett, Brydon L.;Satoh, Yoshitaka. And the article was included in Journal of Medicinal Chemistry in 2021.SDS of cas: 59549-51-8 This article mentions the following:

This manuscript reported the synthesis and structure-activity relationship (SAR) studies for a novel series of JNK inhibitors demonstrating an increased JNK1 bias. SAR optimization on a series of 2,4-dialkylamino-pyrimidine-5-carboxamides, e.g. I resulted in the identification of compounds possessing low nanomolar JNK inhibitory potency, overall kinome selectivity, and the ability to inhibit cellular phosphorylation of the direct JNK substrate c-Jun. Optimization of physicochem. properties in this series resulted in compounds that demonstrated excellent systemic exposure following oral dosing, enabling in vivo efficacy studies and the selection of a candidate for clin. development, CC-90001, which is currently in clin. trials (Phase II) in patients with idiopathic pulmonary fibrosis (NCT03142191). In the experiment, the researchers used many compounds, for example, 5-Bromo-2-chloro-4-(methylthio)pyrimidine (cas: 59549-51-8SDS of cas: 59549-51-8).

5-Bromo-2-chloro-4-(methylthio)pyrimidine (cas: 59549-51-8) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.SDS of cas: 59549-51-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reactions of 6-aminopyrimidin-4(3H)-ones with electron-deficient alkenyl derivatives. Easy preparation of heterocyclic analogs of sangivamycin was written by Cobo, Justo;Sanchez, Adolfo;Nogueras, Manuel. And the article was included in Tetrahedron in 1998.Name: 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one This article mentions the following:

Aminopyrimidinones I (R = H, Me; X = C(OMe):N, C(SMe):N) and uracils I (R = H, Me; X = CONH, CONMe) react with maleic anhydride to give pyrrolopyrimidines II. I (R = H, Me; X = C(OMe):N, C(SMe):N) undergo Michael addition with maleimide to give stable maleimides III (R = H, Me; X = C(OMe):N, C(SMe):N). I (R = Me, X = C(SMe):N) also undergoes a Diels-Alder reaction with maleimide to give 13% of pyrrolopyrimidine IV. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Name: 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Name: 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Solvent-free microwave multicomponent regiospecific synthesis of pyrimido[4,5-c]isoquinolines and evaluation in vitro of their antifungal properties was written by Quiroga, Jairo;Cisneros, Carlos;Insuasty, Braulio;Abonia, Rodrigo;Nogueras, Manuel;Sortino, Maximiliano;Zacchino, Susana. And the article was included in Journal of Heterocyclic Chemistry in 2006.Recommanded Product: 54030-56-7 This article mentions the following:

The solvent-free multicomponent reaction of 6-aminopyrimidin-4(3H)-ones with dimedone and N,N-dimethylformamide dimethylacetal under microwave irradiation yields pyrimido[4,5-c]isoquinolinones. In this process, the intermediate of cyclization was isolated. The structure of the synthesized compounds was determined on the basis of NMR measurements, especially by ¹H,¹H-, ¹H ,¹³C COSY, and DEPT. These compounds showed antifungal in vitro activity particularly against dermatophytes. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Recommanded Product: 54030-56-7).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Recommanded Product: 54030-56-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Accurate Quantification of Sulfonamide Metabolites in Goat Meat: A New Strategy for Minimizing Interaction between Sheep Serum Albumin and Sulfonamide Metabolites was written by Jia, Wei;Zhang, Min;Du, An;Zhang, Rong;Xu, Mudan;Shi, Lin. And the article was included in Journal of Agricultural and Food Chemistry in 2021.Product Details of 1220-83-3 This article mentions the following:

To date, the determination of sulfonamide metabolites in animal-derived food has universal disadvantages of low throughput and no integrated metabolites involved. In this study, a powerful and reliable strategy for high-throughput screening of sulfonamide metabolites in goat meat was proposed based on an aqueous two-phase separation procedure (ATPS) combined with ultrahigh-performance liquid chromatog. quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap). Noncovalent interactions including van der Waals force, hydrogen bonding, and hydrophobic effect were determined to be staple interactions between the sulfonamide metabolites and sheep serum albumin by fluorescence spectroscopy and mol. docking technol., and an 80% acetonitrile-water solution/(NH₄)₂SO₄ was used as ATPS in order to release combined sulfonamide metabolites and minimize the influence of sheep serum albumin. Sulfonamide metabolites in the matrix were screened based on a mechanism of mass natural loss and core structure followed by identification combined with the pharmacokinetic. The developed strategy was validated according to EU standard 2002/657/EC with CCα ranging from 0.07 to 0.98μg kg^-1, accuracy recovery with 84-107%, and RSDs lower than 8.9%. Eighty seven goat meat samples were used for determination of 26 sulfonamides and 8 potential metabolites. On the basis of the established innovative process, this study has successfully implemented the comprehensive detection of sulfonamide metabolites, including N⁴-acetylated substitution, N⁴-hydroxylation, 4-nitroso, azo dimers, oxidized nitro, N⁴ monoglucose conjugation, β-D-glucuronide, and N-4-aminobenzenesulfonyl metabolites, which were shown to undergo oxidation, hydrogenation, sulfation, glucuronidation, glucosylation, and O-aminomethylation. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Product Details of 1220-83-3).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Product Details of 1220-83-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia