Day: February 3, 2023

Discovery of novel and potent PARP/PI3K dual inhibitors for the treatment of cancer was written by Wu, Zhengyang;Bai, Ying;Jin, Jiaming;Jiang, Teng;Shen, Hui;Ju, Qiurong;Zhu, Qihua;Xu, Yungen. And the article was included in European Journal of Medicinal Chemistry in 2021.Recommanded Product: 2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine This article mentions the following:

PARP inhibitors have achieved great success in cancers with BRCA mutations, but only a small portion of patients carry BRCA mutations, which results in their narrow indication spectrum. Recently, emerging evidence has demonstrated that combinations of PARP and PI3K inhibitors could evoke unanticipated synergistic effects in various cancers, even including BRCA-proficient ones. In this work, a series of PARP/PI3K dual inhibitors were designed, synthesized, and evaluated for their biol. activities. It was found that compounds 9a and 23a exhibited excellent inhibitory activities against PARP-1 (9a: IC50 = 1.57 nM, 23a: IC50 = 0.91 nM) and PI3Kα (9a: IC50 = 2.0 nM, 23a: IC50 = 1.5 nM), and showed promising antiproliferative activities against both BRCA-deficient (HCT-116, HCC-1937) and BRCA-proficient (SW620, MDA-MB-231/468) tumor cells. 9a and 23a also exhibited considerable in vivo antitumor efficacy in an MDA-MB-468 xenograft mouse model, with TGI values of 56.39% and 48.77%, resp. Addnl., 23a possessed promising profiles including high kinase selectivity and low cardiotoxicity. Overall, this work indicates 9a and 23a might be potential PARP/PI3K dual inhibitors for cancer therapy and deserve further research. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine (cas: 35265-83-9Recommanded Product: 2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine).

2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine (cas: 35265-83-9) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Recommanded Product: 2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators was written by Chekler, Eugene L. Piatnitski;Unwalla, Rayomond;Khan, Taukeer A.;Tangirala, Raghuram S.;Johnson, Mark;St. Andre, Michael;Anderson, James T.;Kenney, Thomas;Chiparri, Sue;McNally, Chris;Kilbourne, Edward;Thompson, Catherine;Nagpal, Sunil;Weber, Gregory;Schelling, Scott;Owens, Jane;Morris, Carl A.;Powell, Dennis;Verhoest, Patrick R.;Gilbert, Adam M.. And the article was included in Journal of Medicinal Chemistry in 2014.Computed Properties of C7H6Cl2N2O2 This article mentions the following:

We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biol. activity and phys. properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramol. interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating LH (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicol. study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days. In the experiment, the researchers used many compounds, for example, Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate (cas: 171096-33-6Computed Properties of C7H6Cl2N2O2).

Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate (cas: 171096-33-6) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Computed Properties of C7H6Cl2N2O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Response of fungi-microalgae pellets to copper regulation in the removal of sulfonamides and release of dissolved organic matters was written by Li, Shuangxi;Li, Zhuo;Liu, Dongyang;Yin, Zhihong;Hu, Dan;Yu, Yunjiang;Li, Zhaohua;Zhu, Liandong. And the article was included in Journal of Hazardous Materials in 2022.Name: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide This article mentions the following:

Both sulfonamides (SAs) and copper (Cu(II)) were frequently detected together in swine wastewater. In this study, the regulation of Cu(II) on SAs adsorption and release of dissolved organic matters (DOMs) by fungi-microalgae pellets (FM-pellets) were investigated. Aspergillus oryzae pellets were prepared for combination with Chlorella vulgaris and the optimal conditions were at agitation speed of 130 rpm, fungi to microalgae ratio of 10:1 and the combined time of 3 h with the highest combination efficiency of 98.65%. The results showed that adsorption was the main mechanism for SAs removal. FM-pellets exhibited a high SAs adsorption potential within 6 h, and the adsorption capacity of sulfamethazine (SMZ), sulfamonomethoxine (SMM) and sulfamethoxazole (SMX) was 1.07, 0.94 and 1.67 mg/g, resp. Furthermore, the removal of SMX, SMZ and SMM was greatly promoted from 62.31% to 85.21%, 58.71-67.91% and 64.17-80.31%, resp., under the presence of 2 mg/L Cu(II) through ion exchange and adsorption bridging. DOMs were analyzed by the parallel factor (PARAFAC) to demonstrate the response mechanism of FM-pellets to Cu(II). Protein-like substances and NADH in DOMs released by FM-pellets formed complexes with Cu(II) to alleviate the damage on the organism. These findings provide new insights into the mechanism and response of Cu(II) in the removal of SAs by FM-pellets. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Name: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Name: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Determination of organic pollutants in water by off-line supercritical fluid extraction-gas chromatography/infrared spectrometry/mass spectrometry was written by Ren, Li;Wang, Guojun. And the article was included in Sepu in 1998.Category: pyrimidines This article mentions the following:

A supercritical fluid extraction (SFE) method using carbon dioxide for the determination of organic pollutants in Yellow River water was developed. In this paper, organic contaminants in 3L Yellow River water were concentrated on 1g GDX-301 adsorbent and then eluted from the adsorbent with supercritical CO₂. The analytes extracted by SFE were collected into 1mL alc. collecting solvent through a SiO₂ restrictor (35cm x 50μm i.d.). Finally, the collecting solvent was analyzed by Gas Chromatog./IR Spectrometry/Mass Spectrometry. The SFE conditions which were optimized for removal of the analytes from adsorbent were 20MPa, 60°C and 40min. The extraction efficiencies of SFE were directly compared to those obtained by using 15mL dichloromethane elution. Efficiencies of SFE under conditions of 20MPa, 60°C and 40min were generally higher than those of solvent elution. In the experiment, the researchers used many compounds, for example, 4,6-Diphenylpyrimidin-2-amine (cas: 40230-24-8Category: pyrimidines).

4,6-Diphenylpyrimidin-2-amine (cas: 40230-24-8) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Occurrence of veterinary antibiotics in animal manure, compost, and agricultural soil, originating from different feedlots in suburbs of Shanghai, East China was written by Qian, Xiaoyong;Wang, Zhenqi;Zhang, Hongchang;Gu, Hairong;Shen, Genxiang. And the article was included in Environmental Monitoring and Assessment in 2022.Reference of 1220-83-3 This article mentions the following:

The present study aims to monitor and assess the occurrence of veterinary antibiotics (VAs) in animal manure, compost, and fertilized soil, originating from different large-scale feedlots. The corresponding concentrations of 39 types of VAs in 8 large-scale feedlots of pig, dairy cow, and poultry were sampled in different seasons and analyzed using LC-MS. The results indicated that 17 types, 16 types, and 5 types of VAs were detected in the swine manure, compost, and fertilized soil with the concentrations of 0.003-17.82, 0.002-9.59, and 0.004-0.007 mg kg-1 (dry matter), resp.; 3 types, 2 types, and 1 type of VAs were detected in the dairy manure, compost, and fertilized soil with the concentrations of 0.003-1.94, 0.014-0.044, and 0.025 mg kg-1 (dry matter), resp.; 7 types, 5 types, and 1 type of VAs were detected in the poultry manure, compost, and fertilized soil with the concentrations of 0.035-1.06, 0.018-0.049, and 0.019 mg kg-1 (dry matter), resp. The main antibiotic classes persisted in the animal manure and their composting product and fertilized soil were sulfonamides (SAs), macrolides (MAs), and tetracyclines (TCs). Thus, this study would help to adopt strategies in pollution control of VAs and environmental protection of agriculture. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Reference of 1220-83-3).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Reference of 1220-83-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A novel synthesis of guanine PDE inhibitors via tricyclic imidazopyrimidines was written by Gala, Dinesh;DiBenedetto, Donald J.;Kugelman, Max;Mitchell, Michael B.. And the article was included in Tetrahedron Letters in 2003.HPLC of Formula: 54030-56-7 This article mentions the following:

A new method for the preparation of developmental tetracyclic guanine PDE inhibitors via a common tricyclic pyrimidine intermediate is described. Nitration of 6-amino-3-methyl-2-(methylthio)-4(3H)-Pyrimidinone gave 6-amino-3-methyl-2-(methylthio)-5-nitro-4(3H)-Pyrimidinone in 80% yield. Reaction of the latter with (1R,2R)-2-aminocyclopentanol gave rel-6-amino-2-[[(1R,2R)-2-hydroxycyclopentyl]amino]-3-methyl-5-nitro-4(3H)-pyrimidinone. Cyclization of the latter gave (5aR,8aS)-rel-4-amino-1,5a,6,7,8,8a-hexahydro-1-methyl-3-nitro-2H-cyclopent[4,5]imidazo[1,2-a]pyrimidin-2-one (I) as the key intermediate for rel-N-[(5aR,8aS)-4-amino-1,5a,6,7,8,8a-hexahydro-1-methyl-2-oxo-2H-cyclopent[4,5]imidazo[1,2-a]pyrimidin-3-yl]-4-(trifluoromethyl)benzamide (65% yield from I) and rel-N-[(5aR,8aS)-4-amino-1,5a,6,7,8,8a-hexahydro-1-methyl-2-oxo-2H-cyclopent[4,5]imidazo[1,2-a]pyrimidin-3-yl]heptanamide (81% yield from I). These compounds are intermediates for guanine PDE inhibitors (6aR,9aS)-rel-5,6a,7,8,9,9a-hexahydro-5-methyl-2-[[4-(trifluoromethyl)phenyl]methyl]cyclopent[4,5]imidazo[2,1-b]purin-4(1H)-one (Sch 51866) and (6aR,9aS)-rel-2-hexyl-5,6a,7,8,9,9a-hexahydro-5-methylcyclopent[4,5]imidazo[2,1-b]purin-4(1H)-one (Sch 59498). In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7HPLC of Formula: 54030-56-7).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. 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.HPLC of Formula: 54030-56-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

2,4,6-Trisubstituted pyrimidines as a new class of selective adenosine A₁ receptor antagonists was written by Chang, Lisa C. W.;Spanjersberg, Ronald F.;von Kuenzel, Jacobien K.;Mulder-Krieger, Thea;van den Hout, Gijs;Beukers, Margot W.;Brussee, Johannes;Ijzerman, Adriaan P.. And the article was included in Journal of Medicinal Chemistry in 2004.Recommanded Product: 4,6-Diphenylpyrimidin-2-amine This article mentions the following:

Adenosine receptor antagonists usually possess a bi- or tricyclic heteroaromatic structure at their core with varying substitution patterns to achieve selectivity and/or greater affinity. Taking into account mol. modeling results from a series of potent adenosine A₁ receptor antagonists, a pharmacophore was derived from which a monocyclic core can be equally effective. To achieve a compound that may act at the CNS, a restriction related to its polar surface area (PSA) was proposed. In consequence, two series of pyrimidines, e.g., I, possessing good potency at the adenosine A₁ receptor and desirable PSA values were synthesized. In particular, I (LUF 5735) displayed excellent A₁ affinity (K_i = 4 nM) and selectivity (≤50% displacement of 1 μM concentrations of the radioligand at the other three adenosine receptors) and has a PSA value of 53 Ų. In the experiment, the researchers used many compounds, for example, 4,6-Diphenylpyrimidin-2-amine (cas: 40230-24-8Recommanded Product: 4,6-Diphenylpyrimidin-2-amine).

4,6-Diphenylpyrimidin-2-amine (cas: 40230-24-8) 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.Recommanded Product: 4,6-Diphenylpyrimidin-2-amine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The search for a microbiological inhibition method for the rapid, broad-spectrum and high-throughput screening of six kinds of antibiotic residues in swine urine was written by Wu, Qin;Zhu, Qiang;Shabbir, Muhammad Abu Bakr;Sattar, Adeel;Peng, Dapeng;Tao, Yanfei;Chen, Dongmei;Yuan, Zonghui;Wang, Yulian. And the article was included in Food Chemistry in 2021.COA of Formula: C11H12N4O3S This article mentions the following:

In this study, a microbiol. inhibition method for rapidly screening antibiotics in swine urine was established with an easy sample pre-treatment. The microbiol. system consisted of an agar medium mixed with nutrients, sensitizers, a test bacterium (Geobacillus stearothermophilus ATCC12980) and pH indicator (bromocresol purple). It was observed that the detection limits of the test kit for twenty-eight common antimicrobial residues in urine, including β-lactams, aminoglycosides, tetracyclines, sulfonamides, macrolides, and lincosamides, were less than or equal to the maximum residue limits of the kidney, as determined by the EU and China. Moreover, the false neg. rate and the false pos. rate, along with other performance indexes such as interassay coefficients of variation and shelf life of the kit, all met the standard requirements of the ISO13969:2003 guidelines. Addnl., our results were consistent with those using the gold-standard phys. chem. method, which suggest the proposed method is suitable for screening antibiotic residues. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3COA of Formula: C11H12N4O3S).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) 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. 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.COA of Formula: C11H12N4O3S

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Distribution, abundance, and risk assessment of selected antibiotics in a shallow freshwater body used for drinking water, China was written by Kong, Ming;Bu, Yuan-Qing;Zhang, Qin;Zhang, Sheng-Hu;Xing, Li-Qun;Gao, Zhan-Qi;Bi, Feng-Zhi;Hu, Guan-Jiu. And the article was included in Journal of Environmental Management in 2021.Name: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide This article mentions the following:

With rapid improvements in industrialization and urbanization, antibiotics are now extensively used to prevent and treat human and animal diseases and husbandry and aquaculture. Some research has been conducted to assess the environmental distribution and risk level of antibiotics, but their distribution remains largely uncharacterized. Thus, this study investigated the distribution and abundance of 39 antibiotics belonging to five groups, and their associated risks in surface water around Luoma Lake in the north of Jiangsu province, China. Nineteen antibiotics were detected, at a detection frequency (DF) ranging from 2.27% to 100%. The total antibiotics (ΣABs) concentrations ranged from 34.91 to 825.93 ng/L, with a median concentration of 195.45 ng/L. Among these antibiotics, chlortetracycline (DF: 100%; median: 172.02 ng/L) was the dominant antibiotic, accounting for a median percentage of 91.0% of ΣABs concentrations Spearman rank correlation method found a significant correlation between clindamycin (DF: 72.7%; median: 2.01 ng/L) and lincomycin (DF: 79.5%; median: 4.58 ng/L). The ecol. risk quotient (RQ) values for two out of 44 sampling sites were higher than 1, indicating a high risk; 11.4% of the RQ values fell between 0.1 and 1, indicating a medium risk. Moreover, roxithromycin was found to be the dominant contributor to the ecol. risk, accounting for a median of 79.7% of ΣABs. However, the total non-carcinogenic (<6.54 x 10^-4) and carcinogenic risks (<1.64 x 10^-7) of ΣABs were negligible at the detected concentrations In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Name: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide).

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. 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.Name: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bioassay-based identification and removal of target and suspect toxicants in municipal wastewater: Impacts of chemical properties and transformation was written by Liu, Yuan;Li, Faxu;Li, Huizhen;Tong, Yujun;Li, Weizong;Xiong, Jingjing;You, Jing. And the article was included in Journal of Hazardous Materials in 2022.Category: pyrimidines This article mentions the following:

Municipal wastewater contains numerous chems. and transformation products with highly diverse physiochem. properties and intrinsic toxicity; thus, it is imperative but challenging to identify major toxicants. Herein, toxicity identification evaluation (TIE) was applied to identify major toxicants in a typical municipal wastewater treatment plant (WWTP). Impacts of chem. properties on the removal of contaminants and toxicity at individual treatment stages were also examined The WWTP influent caused 100% death of Daphnia magna and zebrafish embryos, and toxicity characterization suggested that organics, metals, and volatiles all contributed to the toxicity. Toxicity identification based on 189 target and approx. one-thousand suspect chems. showed that toxicity contributions of organic contaminants, metals, and ammonia to D. magna were 77%, 4%, and 19%, resp. Galaxolide, pyrene, phenanthrene, benzo[a]anthracene, fluoranthene, octinoxate, silver, and ammonia were identified as potential toxicants. Comparatively, the detected transformation products elicited lower toxicity than their resp. parent contaminants. In contrast, the analyzed contaminants showed negligible contributions to the toxicity of zebrafish embryos. Removal efficiencies of these toxicants in WWTP were highly related to their hydrophobicity. Diverse transformation and removal efficiencies of contaminants in WWTPs may influence the chem. compositions in effluent and ultimately the risk to aquatic organisms in the receiving waterways. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Category: pyrimidines).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) 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. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia