1004-40-6Relevant academic research and scientific papers
An improved synthesis of pyrido[2,3-: D] pyrimidin-4(1 H)-ones and their antimicrobial activity
Fares, Mohamed,Abd El Hadi, Soha R.,Eladwy, Radwa A.,Shoun, Aly A.,Abdel-Aziz, Marwa M.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Keller, Paul A.
, p. 3389 - 3395 (2018)
The screening of a small library of diverse chemical structures resulted in the identification of 2-thioxodihydropyrido[2,3-d]pyrimidine 10a as having broad spectrum antibacterial activity (MIC 0.49-3.9 μg mL-1), and reasonable antifungal activity (MIC 31.25 μg mL-1). An expeditious synthesis of 10a was optimized by varying solvents, catalysts and the use of microwave irradiation with the best conditions using DMF as a solvent, I2 (10 mol%) and a 30 minutes reaction time compared to 15 h for classic conventional heating. The pharmacokinetic properties and calculation of drug likeness of 10a suggested good traditional drug-like properties and led to the synthesis of a small library with seven compounds 10a and 10d-i showing broad antimicrobial activity (MIC = 0.49-7.81 μg mL-1) and selectivity indices of more than 5.6 against the normal colon cell line (CCD-33Co). The antifungal activity of compounds 10d-i was moderate to strong with MIC values of 1.95-15.63 μg mL-1.
[γ-Fe2O3@HAp-SO3H] an efficient nanocatalyst for the synthesis of highly functionalised 2-thioxopyrido[2,3-d]pyrimidines
Mamaghani, Manouchehr,Taati, Zahra,Rasoulian, Mona,Yousefizad, Javad,Toraji, Nooshin,Mohsenimehr, Mona,Nia, Roghayeh Hossein
, p. 29 - 34 (2016)
HAp(hydroxyapatite)-encapsulated-γ-Fe2O3 supported sulfonic acid nanoparticles were used for the preparation of two series of 2-thioxopyrido[2,3-d]pyrimidines. In the first series, 2-thioxopyrido[2,3-d]pyrimidines were synthesised fr
Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold
Elzahabi, Heba S. A.,Nossier, Eman S.,Alasfoury, Rania A.,Khalifa, Nagy M.,El-Manawaty, May A.
, p. 546 - 557 (2018)
An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MC
Convenient synthesis and molecular docking of novel pyrido [2,3-d] pyrimidines as potent antimicrobial candidates
Mohamed, Hanaa S.,Nofal, Zeinab M.,Saleh, Abdulrahman M.,Sarhan, Alaadin E.
, p. 399 - 411 (2021/12/17)
New 3-(3,4-dimethoxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one has been designed as a starting compound to synthesis a novel series of substituted pyrido[2,3-d]pyrimidine system incorporated to different Schiff's bases and enamine derivatives as potent ant
Preparation method of prodrug intermediate of thymidine phosphorylase inhibitor
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Paragraph 0041; 0043-0044; 0049-0052; 0057-0060; 0065-0068, (2021/04/14)
The invention relates to the field of preparation of prodrug intermediates of thymidine phosphorylase inhibitors, and discloses a preparation method of a prodrug intermediate of a thymidine phosphorylase inhibitor. The method comprises the following steps: (1) adding ethyl cyanoacetate into a mixed alcoholic-alkaline solution of thiourea, carrying out reflux reaction for 5-6 hours, performing cooling, crystallizing, filtering, and washing with an ethanol/dioxane mixed solution; (2) mixing pyridine with ammonia water, adding Raney nickel, ZnSO4 and the product obtained in the step (1), heating and reacting at 65-75 DEG C for 7-8 hours, performing filtering while the product is hot, and performing cooling and crystallizing, filtering and washing; and (3) adding the product obtained in the step (2) into a mixed alkali solution, slowly adding 2-bromoacetaldehyde at 45-55 DEG C, reacting for 4-5 hours, and performing cooling, crystallizing, filtering, washing and drying. According to the preparation method disclosed by the invention, the total yield of the prodrug intermediate 4-hydroxypyrrolo[2, 3-d] pyrimidine of the thymidine phosphorylase inhibitor is improved.
Production process 4 -chloropyrrolo [2, 3 - d] pyrimidine
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Paragraph 0108-0110, (2021/10/27)
The production process of 4 - chloropyrrolo [2, 3 - d] pyrimidine comprises the following steps: S1, adding the compound I and the compound II to the mixed solvent I, carrying out temperature rise reaction under the catalysis of the base I to obtain the compound III. S2, sodium alkoxide I was added to alcoholic solvent II, compound IV and compound III were added to raise the temperature, and organic solvent III, organic solvent IV and compound V were added to raise the temperature to give 4 - chloropyrrolo [2, 3 - d] pyrimidine crude product. Among them, compound I is. . Compound II was obtained. . Compound III was obtained. . The compound IV is formamidine. Compound V was POCl. 3 To the method, bromoacetaldehyde dimethyl acetal and cyanoethyl acetate are subjected to reflux reaction, and 2 - cyano -4, 4 - methoxybutyric acid ethyl ester and formamidine acetate are subjected to one-pot chlorofluorination reaction, so that the reaction period is greatly shortened.
Discovery and evaluation of new compounds targeting ribosomal protein S1 in antibiotic-resistant Mycobacterium Tuberculosis
Dai, Yazhuang,Guo, Chenyun,Lin, Donghai,Lin, Kejiang,Xu, Yinqiu,Xue, Xiaowen
, (2020/04/20)
The emergence of antibiotic-resistant Mycobacterium Tuberculosis (Mtb) infections compels new treatment strategies, of which targeting trans-translation is promising. During the trans-translation process, the ribosomal protein S1 (RpsA) plays a key role, and the Ala438 mutant is related to pyrazinamide (PZA) resistance, which shows its effects after being hydrolysed to pyrazinoic acid (POA). In this study, based on the structure of the RpsA C-terminal domain (RpsA-CTD) and POA complex, new compounds were designed. After being synthesized, the compounds were tested in vitro with saturation transfer difference (STD), fluorescence quenching titration (FQT) and chemical shift perturbation (CSP) experiments. Finally, six of the 17 new compounds have high affinity for both RpsA-CTD and its Ala438 deletion mutant. The active compounds provide new choices for targeting trans-translation in Mtb, and the analysis of the structure-activity relationships will be helpful for further structural modifications based on derivatives of 2-((hypoxanthine-2-yl)thio)acetic acid and 2-((5-hydroxylflavone-7-yl)oxy)acetamide.
PB-10, a thiazolo[4,5-d] pyrimidine derivative, targets p21-activated kinase 4 in human colorectal cancer cells
Li, Ruijuan,Wang, Hanxun,Wang, Jian,Cheng, Maosheng
, (2019/11/26)
Targeting p21-activated kinase 4 (PAK4) is a potential therapeutic strategy against human colorectal cancer (CRC). In this study, we synthesized a series of novel thiazolo[4,5-d]pyrimidine derivatives (PB-1–12) and identified PB-10 (PAK4 IC50 = 15.12 μM) as a potential and potent PAK4 inhibitor. Our results showed that PB-10 significantly suppressed the proliferation and colony formation of human CRC cells. PB-10 also arrested HCT-116 CRC cells at sub G0/G1 phase while promoting the expression of proapoptotic proteins. In addition, PB-10 inhibited migration, invasion, and adhesion as well as the PAK4 downstream signaling pathway in HCT-116 cells. Molecular docking analysis showed possible binding modes between PB-10 and PAK4. Our study provides a novel compound that may block the PAK4 signaling in CRC cells.
Pyrimidinone derivative, preparation method thereof and application thereof in resisting mycobacterium tuberculosis infection
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Paragraph 0148-0150, (2020/11/25)
The invention discloses a pyrimidinone derivative, a preparation method thereof and an application thereof in resisting mycobacterium tuberculosis infection. The structure of the pyrimidinone derivative is shown as a formula I, wherein R1, m, X, Y, Z, R2
Synthesis, experimental and computational studies of N-(4-amino-6-oxo-1,6-dihydropyrimidin-5-yl)benzamide
Kaczor, Agnieszka A.,Bartyzel, Agata,Pitucha, Monika,Wróbel, Tomasz M.,Wo?niak, Sylwia,Matosiuk, Dariusz
, p. 491 - 502 (2019/05/01)
Background: Blockade of kainate receptors is an emerging strategy to treat neurodegenera-tive diseases, including Parkinson’s disease as well as to treat epilepsy. In particular, non-competitive antagonists of kainate receptors are promising due to the expected good safety profile. We present here synthesis, experimental and computational studies of N-(4-amino-6-oxo-1,6-dihydropyrimidin-5-yl)benzamide which is an intermediate in the synthesis of hypoxanthine derivatives which were designed as non-competitive antagonists of kainate GluK1/GluK2 receptors. Method: The title compound was obtained in a five-step synthesis protocol and characterized used X-ray crystallography and experimental and computed spectra. Results: The presented detailed X-ray studies of the title compound confirm the reaction course. The title compound crystallizes in triclinic P-1 space group. The asymmetric unit comprises two independent molecules of the compound (A and B) and a DMF solvent molecule. The interpretation of IR spectra was facilitated by Potential Energy Distribution (PED) analysis. The low value of HOMO-LUMO gap indicates that the studied compound is relatively reactive. Conclusion: The title compound is a well-characterized intermediate which will be subjected to cycli-zation to hypoxanthine derivative designed as non-competitive antagonist of kainate GluK1 and GluK2 receptors.
