Day: January 30, 2023

Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy was written by Banerjee, Souvik;Arnst, Kinsie E.;Wang, Yuxi;Kumar, Gyanendra;Deng, Shanshan;Yang, Lei;Li, Guo-bo;Yang, Jinliang;White, Stephen W.;Li, Wei;Miller, Duane D.. And the article was included in Journal of Medicinal Chemistry in 2018.Computed Properties of C7H4Cl2N2S This article mentions the following:

We report the design, synthesis, and biol. evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Addnl., for the first time, we report high-resolution X-ray crystal structures for the best compounds in this scaffold. These structures not only confirm their direct binding to the colchicine site in tubulin and reveal their detailed mol. interactions but also contrast the previously published proposed binding mode. Compounds I and II significantly inhibited tumor growth in an A375 melanoma xenograft model and were accompanied by elevated levels of apoptosis and disruption of tumor vasculature. Finally, we demonstrated that compound I significantly overcame clin. relevant multidrug resistance in a paclitaxel resistant PC-3/TxR prostate cancer xenograft model. Collectively, these studies provide preclin. and structural proof of concept to support the continued development of this scaffold as a new generation of tubulin inhibitors. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine (cas: 35265-83-9Computed Properties of C7H4Cl2N2S).

2,4-Dichloro-7-methylthieno[3,2-d]pyrimidine (cas: 35265-83-9) 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.Computed Properties of C7H4Cl2N2S

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The design and synthesis of thrombin inhibitors: analogues of MD805 containing non-polar surrogates for arginine at the P1 position was written by Baettig, U.;Brown, L.;Brundish, D.;Dell, C.;Furzer, A.;Garman, S.;Janus, D.;Kane, P. D.;Smith, G.;Walker, C. V.;Cockcroft, X.;Ambler, J.;Mitchelson, A.;Talbot, M. D.;Tweed, M.;Wills, N.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2000.Electric Literature of C4H5N3O This article mentions the following:

A series of monocyclic and bicyclic amino acids have been synthesized and incorporated into thrombin inhibitors based on CGH728, an analog of the Mitsubishi compound MD805. Benzthiazolylalanine (Bta) was a good non-polar substitute for arginine at the P1 position, yielding compounds with low nanomolar potency and good selectivity for thrombin. In the experiment, the researchers used many compounds, for example, 5-Aminopyrimidin-4(3H)-one (cas: 69785-94-0Electric Literature of C4H5N3O).

5-Aminopyrimidin-4(3H)-one (cas: 69785-94-0) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. 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.Electric Literature of C4H5N3O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Suspect screening and untargeted analysis of veterinary drugs in food by LC-HRMS: Application of background exclusion-dependent acquisition for retrospective analysis of unknown xenobiotics was written by Zhu, Chunyan;Lai, Guoyin;Jin, Ying;Xu, Dunming;Chen, Jiayun;Jiang, Xiaojuan;Wang, Suping;Liu, Guoqiang;Xu, Niusheng;Shen, Rong;Wang, Luxiao;Zhu, Mingshe;Wu, Caisheng. And the article was included in Journal of Pharmaceutical and Biomedical Analysis in 2022.Recommanded Product: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide This article mentions the following:

The presence of veterinary drug and pesticide residues in food products pose considerable threats to human health. Monitoring of these residues in food is mainly carried out using targeted anal. by triple quadrupole mass spectrometry. However, these methods are not suitable for suspect screening and untargeted anal. of unknowns. The main objectives of this study were to develop a new high-resolution mass spectrometry (HRMS)-based anal. strategy for retrospective anal. of suspect and unknown xenobiotics and to evaluate its performance in the tentative identification of 48 veterinary drugs as “unknowns” spiked in a pork sample. In the anal., a newly developed background exclusion data-dependent acquisition (BE-DDA) technique was employed to trigger the product ion (MS/MS) spectral acquisition of the “unknowns”, and an inhouse precise-and-thorough background-subtraction (PATBS) technique was applied to detect these “unknowns”. Showed that untargeted data mining of the acquired LC-MS dataset by PATBS was able to find all the 48 veterinary drugs and 46 of them were triggered by BE-DDA to generate accurate MS/MS spectra. The dataset of recorded accurate full-scan mass and MS/MS spectra of all the xenobiotics of the test pork sample is defined as the xenobiotics profile. Searching the xenobiotic profile of the test pork sample using mass spectral data of selected veterinary drugs (as suspects) from the mzCloud spectral library led to the correct hits. Searching against the mzCloud spectral library using the mass spectral data of selected individual veterinary drugs (as unknowns) from the xenobiotics profile tentatively confirmed their identities. In contrast, anal. of the same sample using ion intensity-data dependent acquisition only recorded the MS/MS spectra for 34 veterinary drugs. In addition, a data independent acquisition method enabled the acquisition of the fragment spectra for 44 veterinary drugs, but their spectral data displayed only one or a few true product ions of individual analytes of interest along with many fragments from coeluted biol. components and background noises. This study demonstrates that this anal. strategy has a potential to become a practical tool for the retrospective suspect screening and untargeted anal. of unknown xenobiotics in a biol. sample such as veterinary drugs and pesticides in food products. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Recommanded Product: 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. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Recommanded Product: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cropping system exerts stronger influence on antibiotic resistance gene assemblages in greenhouse soils than reclaimed wastewater irrigation was written by Liu, Yuan;Neal, Andrew L.;Zhang, Xiaoxian;Fan, Haiyan;Liu, Honglu;Li, Zhongyang. And the article was included in Journal of Hazardous Materials in 2022.Category: pyrimidines This article mentions the following:

The effects of reclaimed wastewater (RW) irrigation on the spread of antibiotic resistance genes (ARGs) in soil is modulated by a myriad of biotic and abiotic factors and their relative significance remains vague. We compared microbial communities, assemblages of genes associated with microbial resistance to antibiotics, biocides and metals, and insertion sequences (ISs) in soils following 16 years of irrigation with groundwater (GW), RW or alternately with GW and RW in two greenhouses with different cropping systems, using shotgun metagenome sequencing. The results showed that cropping system exerted greater influence than irrigation on the profile of ISs and resistance genes. This influence was most strongly associated with concentrations of copper, mercury and perfloxacin in the soils. There was no significant difference in soil ARG profiles between continuous RW irrigation and alternating GW and RW irrigation. Proteobacteria, Actinobacteria and Firmicutes and a limited number of ISs were closely associated with the detected ARGs. Most ARGs were found to co-occur with metal and biocide resistance genes through the mechanism of efflux pumps. These findings highlight the significance of understanding and improving crop management in mitigating the dissemination of ARGs in soils irrigated with RW. 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. 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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Changes of antibiotic occurrence and hydrochemistry in groundwater under the influence of the South-to-North Water Diversion (the Hutuo River, China) was written by Wang, Jialin;Zhang, Chong;Xiong, Ling;Song, Guangdong;Liu, Fei. And the article was included in Science of the Total Environment in 2022.Computed Properties of C11H12N4O3S This article mentions the following:

The occurrence of antibiotics in groundwater has significant spatial variability, owing to the complexity of pollutant properties, pollution sources and groundwater recharge and discharge conditions. This study aimed to identify the relationship between antibiotic occurrence and hydrochem. in groundwater. Thus, we undertook this study in a characteristic alluvial-diluvial aquifer where groundwater receives unidirectional recharge from surface water. In total, 47 samples were collected from the Hutuo River before and after an artificial replenishment project. We screened up to four classes of antibiotics and detected 28 types. The statistical anal. of antibiotic concentrations, indicated that there were two pollution areas. Next, we discussed the results pertaining to the occurrence and source of antibiotics by comparing them with hydrochem. data. In the study area, a pos. correlation has been found between inorganic compounds, as SO₄^2-and Cl^–, and the most mobile antibiotics given that both share the same source. This shows that a previous sound geochem. study may provide evidence of the extend of antibiotic occurrence, as in the Hutuo River aquifer. The relationship between antibiotics and hydrochem. in groundwater is determined by recharge sources (rainwater and surface water contaminated with antibiotics). Antibiotics from wastewater treatment plants enter groundwater indirectly through surface water with high SO₄^2- in lightly polluted areas, while in heavily polluted areas, there are high concentrations of inorganic components in garbage leachate and wastewater leakage that carry antibiotics directly into groundwater. In summarized, the relationship between antibiotics and hydrochem. observed in this study shows that a previous sound geochem. study may provide evidence of the extend of antibiotic occurrence. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Computed Properties of C11H12N4O3S).

4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Computed Properties of C11H12N4O3S

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part II was written by Das, Sanjib;Shelke, Dnyaneshwar E.;Harde, Rajendra L.;Avhad, Vijayshree B.;Khairatkar-Joshi, Neelima;Gullapalli, Srinivas;Gupta, Praveen K.;Gandhi, Maulik N.;Bhateja, Deepak K.;Bajpai, Malini;Joshi, Ashwini A.;Marathe, Megha Y.;Gudi, Girish S.;Jadhav, Satyawan B.;Mahat, Mahamad Yunnus A.;Thomas, Abraham. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2014.Name: 4-(2-Chloropyrimidin-4-yl)morpholine This article mentions the following:

We report the design and synthesis of novel pyrrolo[3,2-b]quinoline containing heteroarene ethers as PDE10A inhibitors with good to excellent potency, selectivity and metabolic stability. Further optimization of this primary series resulted in the identification of 1-methyl-3-(4-{[3-(pyridine-4-yl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrolo[3,2-b]pyridine (I) with good hPDE10A potency (IC₅₀: 6.3 nM), excellent selectivity over other related PDEs, and desirable physicochem. properties. The compound exhibited high peripheral and adequate brain levels upon oral dosing in rodents. The compound also showed excellent efficacy in multiple preclin. animal models related to psychiatric disorders, particularly schizophrenia. In the experiment, the researchers used many compounds, for example, 4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0Name: 4-(2-Chloropyrimidin-4-yl)morpholine).

4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0) 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.Name: 4-(2-Chloropyrimidin-4-yl)morpholine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis of new 6-aroylpyrido[2,3-d]pyrimidines was written by Quiroga, Jairo;Viveros, German;Insuasty, Braulio;Nogueras, Manuel;Sanchez, Adolfo;Cobo, Justo. And the article was included in Journal of Heterocyclic Chemistry in 1999.Computed Properties of C6H9N3OS This article mentions the following:

The synthesis of 6-dimethylaminomethylenaminopyrimidin-4(3H)-ones (2) and its reaction with β-dimethylaminopropiophenone hydrochloride (3) is discussed. The reaction of 6-aminopyrimidin-4(3H)-ones with an excess of DMF di-Me acetal gives 6-dimethylaminomethyleneaminopyrimidines 2. Heating of equimol. quantities of 2 and 3 in DMF leads to 6-aroylpyrido[2,3-d]pyrimidine derivatives In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Computed Properties of C6H9N3OS).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Computed Properties of C6H9N3OS

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Highly efficient, chemoselective syntheses of 2-methoxy-4-substituted pyrimidines was written by Xu, Chunyan;Cheng, Chuanjie;Liu, Hongtao;Liu, Bo. And the article was included in Letters in Organic Chemistry in 2011.Category: pyrimidines This article mentions the following:

Three 2-methoxy-4-substituted pyrimidine compounds were chemoselectively synthesized by diazotization, using 2,4-dichloropyrimidine as the starting material. In nonaqueous diazotization reaction system, halo-substituted I (X = Br, Cl) were efficiently prepared, and in aqueous medium, hydrolysis product I (X = OH) was afforded. In the experiment, the researchers used many compounds, for example, 4-Chloro-2-methoxypyrimidine (cas: 51421-99-9Category: pyrimidines).

4-Chloro-2-methoxypyrimidine (cas: 51421-99-9) 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. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Solution-phase parallel synthesis using ion-exchange resins was written by Suto, Mark J.;Gayo-Fung, Leah M.;Palanki, Moorthy S. S.;Sullivan, Robert. And the article was included in Tetrahedron in 1998.Recommanded Product: Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate This article mentions the following:

Ion-exchange resins are useful as scavengers in solution-phase parallel synthesis. Ester and amide libraries have been generated using basic ion-exchange resins to facilitate the formation of products and to remove reaction byproducts. Acidic ion-exchange resins have been used as selective amine scavengers in the synthesis of urea and amine libraries. Several compound libraries have been prepared using the basic ion-exchange resin Amberlyst 21 as part of our lead optimization program. The utility of ion-exchange resins as a means of generating both large and small focused libraries is reviewed. In the experiment, the researchers used many compounds, for example, Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate (cas: 187035-79-6Recommanded Product: Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate).

Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate (cas: 187035-79-6) 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.Recommanded Product: Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Molybdenum disulfide (MoS₂): A novel activator of peracetic acid for the degradation of sulfonamide antibiotics was written by Wang, Jingwen;Wang, Zongping;Cheng, Yujie;Cao, Lisan;Bai, Fan;Yue, Siyang;Xie, Pengchao;Ma, Jun. And the article was included in Water Research in 2021.Recommanded Product: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide This article mentions the following:

Sulfonamide antibiotics (SAs) are typical antibiotics and have attracted increasing concerns about their wide occurrence in environment as well as potential risk for human health. In this study, we applied a novel advanced oxidation process in SAs degradation by combining molybdenum sulfide and peracetic acid (MoS₂/PAA). Reactive oxygen species (ROS) including HO•, CH₃C(O)O•, CH₃C(O)OO•, and ¹O₂ were generated from PAA by MoS₂ activation and contributed to SAs degradation The effects of initial pH, the dosages of PAA and MoS₂, and humic acid for SAs degradation were further evaluated by selecting sulfamethoxazole (SMX) as a target SA in the MoS₂/PAA process. Results suggested that the optimum pH for SMX removal was 3, where the degradation efficiency of SMX was higher than 80% after reaction for 15 min. Increasing PAA (0.075-0.45 mM) or MoS₂ (0.1-0.4 g/L) dosages facilitated the SMX degradation, while the presence of humic acids retarded the SMX removal. This MoS2/PAA process also showed good efficiencies in removing other SAs including sulfaguanidine, sulfamonomethoxine and sulfamerazine. Their possible degradation pathways were proposed based on the products identification and DFT calculation, showing that apart from the oxidation of amine groups to nitro groups in SAs, MoS₂/PAA induced SO₂ extrusion reaction for SAs that contained six-membered heterocyclic moieties. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Recommanded Product: 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. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Recommanded Product: 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia