5147-80-8Relevant academic research and scientific papers
Synthesis of Polysubstituted Pyrimidines from Ketene Dithioacetals Using KF/Al2O3 Catalyst
Yu, Shen-Yi,Cai, Ya-Xian
, p. 3989 - 3995 (2003)
KF/Al2O3 was first used to catalyze the synthesis of 2-alkylthio-4-amino-5-cyano-6-methylthiopyrimidines 3a-f via the reaction of the ketene dithioacetals 1 (prepared from malononitrile) with isothiuronium salts 2a-f. Six pyrimidine compounds were prepared and all of their structures were confirmed by elemental analysis, 1H NMR, and IR. The reaction conditions (solvents, catalyst amounts, and temperature) were investigated for the first time. The separation yield reached 89%.
Preparation method and use of thiophene compound
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Paragraph 0105; 0106, (2020/02/17)
The invention belongs to the technical field of pharmaceutical chemistry, and relates to thiophene compounds shown by general formula I, pharmaceutically acceptable salts, solvates or prodrugs and preparation methods thereof. In which substituents L, Ar, R have the meanings given in the specification. The invention also relates to a strong PI3K inhibitory effect of a compound of the general formula I, and also relates to the use of such compounds and pharmaceutically acceptable salts, solvates or prodrugs thereof in the preparation of drugs for the treatment and/or prevention of diseases caused by abnormally high expression of PI3K, in particular in the preparation of drugs for the treatment and/or prevention of cancer.
Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors
Adhikari, Sharmila,Brownell, James E.,Calderwood, Emily F.,Chouitar, Jouhara,D'Amore, Natalie Roy,England, Dylan B.,Foley, Klaudia,Gould, Alexandra E.,Harrison, Sean J.,Huang, Shih-Chung,LeRoy, Patrick J.,Lok, David,Lublinsky, Anna,Ma, Li-Ting,Menon, Saurabh,Yang, Yu,Zhang, Ji
, (2020/08/13)
Autophagy is postulated to be required by cancer cells to survive periods of metabolic and/or hypoxic stress. ATG7 is the E1 enzyme that is required for activation of Ubl conjugation pathways involved in autophagosome formation. This article describes the design and optimization of pyrazolopyrimidine sulfamate compounds as potent and selective inhibitors of ATG7. Cellular levels of the autophagy markers, LC3B and NBR1, are regulated following treatment with these compounds.
Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity
Chen, Rui,Gong, Guowei,Han, Yufei,Lei, Qiancheng,Liao, Weike,Liu, Jiaan,Qi, Yinliang,Sun, Ming,Tang, Lei,Tian, Ye,Wang, Zhongyuan,Xie, Juan,Zhao, Yanfang
supporting information, (2020/05/05)
Using a rational design strategy for isoform-selective inhibition of PI3Kα, two series of novel 2,3,4,5-tetra-substituted thiophene derivatives containing either diaryl urea or N-Acylarylhydrazone scaffold were designed and synthesized. The most promising compound 12k was demonstrated to bear nanomolar PI3Kα inhibitory potency with 12, 28, 30, 196-fold selectivity against isoforms β, γ, δ and mTOR. Besides, it also showed good developability profiles in cell-based proliferation against a panel of human tumor cells as well as ADME assays. We herein report on their design, synthesis, SAR and potential developability properties.
Tailored-design Synthesis of Sulfapyrimidine Derivatives
Azzam, Rasha A.
, p. 619 - 627 (2019/01/04)
In this paper, we report an efficient and convenient approach for the synthesis of tailored-design target sulfapyrimidine derivatives expected to show remarkable antimicrobial activities. The approach is based on reacting arylsulfonyl guanidine with α,β-unsaturated carbonyl compounds to afford N-(4,6-diarylpyrimidin-2-yl)arylsulfonamide or with ylidene derivatives to afford N-(6-aryl-5-cyanopyrimidin-2-yl)arylsulfonamide, N-(4-amino-5-cyano-6-(methylthio)-pyrimidin-2-yl)-arylsulfonamide, and N-(5-cyanopyrimidin-2-yl)arylsulfonamide compounds through Michael addition reaction. The structure of the newly synthesized compounds was confirmed from spectral data and elemental analysis.
Reactions of ketene dithioacetal for a new versatile synthesis of 4,5-substituted 3-aminothiophene-2-carboxylate derivatives
Chavan, Satish M.,Toche, Raghunath B.,Patil, Vasant M.,Aware, Pankaj B.,Patil, Poonam S.
, p. 426 - 437 (2016/07/23)
ABSTRACT: Poly substituted 3-aminothiophenes were successfully synthesized in good yields by using a one-pot protocol via ketene S,S-acetal as an intermediate in basic medium (K2CO3/N,N-dimethylformamide) followed by Dieckmann condensation with ethyl bromoacetate. Further, chemistry of thiophenes was explored using active functional groups such as C3–NH2, C4–CN and C5–SCH3 on the thiophene nucleus. Synthesis of ethyl 3-acetamido-4-cyano-5-(methylthio)thiophene-2-carboxylate derivatives and ethyl 3-amino-4-carbamoyl-5-(methylthio)thiophene-2-carboxylate derivatives.
Synthesis, structural characterization of some pyrazolo [3,4-d] pyrimidine derivatives as anti-inflammatory agents
Abd El-Salam,Zaki,Said,Abdulla
, p. 529 - 547 (2014/04/03)
A SERIES of pyrimidine and fused triazolopyrimidine derivatives were newly synthesized using aminopyrazole carbonitrile 1 as a had starting material and compounds 14 and 16 are intermediates. Initially, the acute toxicity of the compounds was assayed via the determination of their LD50, and all compounds were interestingly less toxic and had lower ulcerogenic activities than Diclophenac as a reference drug. Regarding the protection against Carrageenan induced edema; the pharmacological screening showed that compounds 17, 11, 13 and 5 have good anti-inflammatory activities comparable to the reference drug. On the other hand, in searching for COX-2 inhibitor, the inhibition of plasma prostaglandine (PGE2) for the compounds was determined and the same four compounds were found the more potent agents. The detailed synthesis, spectroscopic data, pharmacological screening and acute toxicity LD50 for the synthesized compounds were reported.
Tin tetrachloride-catalyzed regiospecific allylic substitution of quinone monoketals: An easy entry to benzofurans and coumestans
Liu, Yingjie,Liu, Jingxin,Wang, Mang,Liu, Jun,Liu, Qun
supporting information, p. 2678 - 2682 (2013/01/15)
A highly regioselective allylic substitution of quinone monoketals with a-oxoketene dithioacetals is achieved under the catalysis of only tin tetrachloride (1 mol%). The advantages of the reaction, including its simplicity, rapidity, low catalyst loading of inexpensive tin tetrachloride, mild conditions and; in particular, the regiospecificity, is proposed to be due to a pseudo-intramolecular process. This new synthetic method provides a facile [3+2] cycloaddition route to benzofurans and is highlighted by the synthesis of coumestans.
Development of scalable syntheses of selective PI3K inhibitors
Huang, Qinhua,Richardson, Paul F.,Sach, Neal W.,Zhu, Jinjiang,Liu, Kevin K.-C.,Smith, Graham L.,Bowles, Daniel M.
experimental part, p. 556 - 564 (2011/12/02)
On the basis of a more practical and scalable route to an iodothiophene, an efficient and reliable synthesis has been developed for three selective PI3K inhibitors. From this advanced intermediate, the three title compounds were each prepared in five additional steps. Key learnings also include: high throughput experimentation (HTE) screening toward a more robust Suzuki coupling, a more efficient triazole synthesis, and an acid/base cleanup developed to purify the final compounds. The final enabled synthesis required no column chromatography.
SNAr and palladium-catalyzed reactions of deactivated thiophene: Application to the synthesis of protein farnesyltransferase inhibitors
Lethu, Sebastien,Dubois, Joelle
experimental part, p. 3920 - 3931 (2011/09/14)
To investigate the influence of the 5-thioether moiety of our previously identified hit thiophene compound upon protein farnesyltransferase inhibition, we synthesized a new library of 3-(4-chlorophenyl)-4-cyanothiophene-2-carboxylic derivatives through the application of aromatic nucleophilic substitutions benefiting from a sulfone-based leaving group and by direct palladium-catalyzed reactions on a thioalkylthiophene. This small library of ester derivatives and their corresponding acids was then evaluated for protein farnesyltransferase inhibitory activity; some library members exhibited promising submicromolar activities. Copyright
