17823-65-3Relevant academic research and scientific papers
Utility of bis(methylthio)methylene malononitrile as a synthon in the synthesis of new poly-functionalized cyanoiminopyrimidines
Moustafa, Amr Hassan,Amer, Amer Anwar
, p. 2129 - 2134 (2017)
Abstract: A new series of 4-(alkyl/arylamino)-6-amino-5-cyano-2-cyanoimino-1H-pyrimidine was obtained via one-pot three-component reaction of bis(methylthio)methylene malononitrile, primary amines, and cyanoguanidine using sodium ethoxide as basic catalys
One-Pot Synthesis and Antiproliferative Activity of Highly Functionalized Pyrazole Derivatives
Iervasi, Erika,Lusardi, Matteo,Ponassi, Marco,Rosano, Camillo,Rotolo, Chiara,Spallarossa, Andrea
, (2022/02/05)
A series of highly functionalized pyrazole derivatives has been prepared by a one-pot, versatile and regioselective procedure. Pyrazoles 1–29 were tested in cell-based assay to assess their antiproliferative activity against a panel of tumour cells. Addit
Design, Synthesis, biological Evaluation, and molecular docking studies of novel Pyrazolo[3,4-d]Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers
Bayoumi, Ashraf H.,El-Morsy, Ahmed M.,Hagras, Mohamed,Sherbiny, Farag F.,Sobhy, Mohamed
, (2021/09/10)
A series of novel hybrid pyrazolo[3,4-d]pyramidine derivatives was designed and chemically synthesized in useful yields. The synthesized compounds were structurally characterized by the usual techniques. All the new synthesized compounds were biologically screened in vitro for their antiproliferative activities against a panel of four cancer cell lines, namely HepG-2, MCF-7, HCT-116, and Hela. The results of cytotoxic evaluation indicated that compound 14d was appeared to be the most prominent broad-spectrum cytotoxic activity and significantly more potent than sorafenib with IC50 values of 4.28, 5.18, 3.97, and 9.85 μM against four cell lines (HePG2, Hela, HCT-116 and MCF-7). In addition, compound 15 was displayed promising antiproliferative effect against all tested cell lines with IC50 value less than 11 μM compared with sorafenib as a control drug. Besides, structurally pharmacophoric features indicated that pyrazolo[3,4-d]pyrimidine scaffold having an amide linker and substituted with phenyl moiety at the 5-position was more potent than those possessing azomethine methyl, azomethine proton and carbomethene linkers, which lead to significant decrease in antiproliferative activity. The most potent compounds were further selected and evaluated for their activities against epidermal growth factor receptor (EGFR) kinase inhibitors according to homogenous time resolved fluorescence (HTRF) assay. The most potent compound 14d exhibited the most promising inhibitory activity against EGFRWT with IC50 value of 56.02 ± 1.38 μM compared with gefitinib as control drug with IC50 value of 41.79 ± 1.07 μM. Moreover, the inhibition of cell cycle progression and induction of apoptosis in the A549 cell line at G2/M and pre-G1 phases of cell cycle might contribute to cancer treatment that evaluated by Annexin V-FITC/PI double staining detection method. Finally, molecular docking studies were conducted to investigate that probable binding conformations of these anticancer agents and ADME properties were calculated to predict pharmacokinetics and toxic properties of the target compounds.
Triflic acid-mediated N-heteroannulation of β-anilino-β-(methylthio)acrylonitriles: a facile synthesis of 4-amino-2-(methylthio)quinolines
Bandyopadhyay, Debashruti,Panigrahi, Adyasha,Peruncheralathan, S.,Radhakrishnan, Divya,Thirupathi, Annaram
supporting information, p. 8544 - 8553 (2021/10/20)
Various functionalised 4-amino-2-(methylthio)quinolines are synthesised through triflic acid-mediated N-heteroannulation of α-functionalized-β-anilino-β-(methylthio)acrylonitriles for the first time. The N-heteroannulation process is highly chemoselective and has mild reaction conditions. However, this process fails in the absence of the β-methylthio group in the acrylonitriles. In addition, a new double N-heteroannulation process is demonstrated to synthesise indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine is synthesised in four steps from an acyclic precursor.
Application of malononitrile compound as bactericide
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Paragraph 0296, (2020/08/18)
The invention discloses an application of a malononitrile compound represented by a general formula I as a bactericide, wherein substituents in the formula are defined in the specification. The compound represented by the general formula I has excellent a
From Carbodiimides to Carbon Dioxide: Quantification of the Electrophilic Reactivities of Heteroallenes
Li, Zhen,Mayer, Robert J.,Ofial, Armin R.,Mayr, Herbert
supporting information, p. 8383 - 8402 (2020/05/22)
Kinetics of the reactions of isocyanates, isothiocyanates, carbodiimides, carbon disulfide, and carbon dioxide with carbanions or enamines (reference nucleophiles) have been measured photometrically in acetonitrile or DMSO solution at 20 °C. The resulting second-order rate constants and the previously published reactivity parameters N and sN of the reference nucleophiles were substituted into the correlation log k2(20 °C) = sN(N + E) to determine the electrophilicity parameters of the heteroallenes: TsNCO (E = -7.69) ? PhNCO (E = -15.38) > CS2 (E = -17.70) ≈ PhNCS (E = -18.15) > PhNCNPh (E = -20.14) ? CyNCNCy (E ≈ -30). An approximate value could be derived for CO2 (-16 E - 11). Quantum chemical calculations were performed at the IEFPCM(DMSO)/B3LYP-D3/6-311+G(d,p) level of theory and compared with experimental Gibbs activation energies. The distortion-interaction model was used to rationalize the different reactivities of O- and S-substituted heteroallenes. Eventually it is demonstrated that the electrophilicity parameters determined in this work can be used as ordering principle for literature-known reactions of heteroallenes.
Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity
Ali, Ghada M.E.,Ibrahim, Diaa A.,Elmetwali, Amira M.,Ismail, Nasser S.M.
, p. 1 - 14 (2019/01/26)
Different series of novel pyrazole and pyrazolo[1,5-a] pyrimidine derivatives (2a-g), (3a-c), (7a-d) and (10a-e) were designed, synthesized and evaluated for their ability to inhibit CDK2/cyclin A2 enzyme in vitro. In addition, the cytotoxicity of the newly synthesized compounds was screened against four different human cancer cell lines. The CDK2/cyclin A2 enzyme inhibitory activity revealed that compounds (2d) and (2 g) are among the most active with inhibitory activity values of 60% and 40%, respectively, while compounds (7d) and (10b) exhibited the highest activity among the newly synthesized derivatives against four tumor cell lines (HepG2, MCF-7, A549 and Caco2) with IC50 values 24.24, 14.12, 30.03 and 29.27 μM and 17.12, 10.05, 29.95 and 25.24 μM, respectively. Flow cytometry cell cycle assay was carried for compounds (7d) and (10b) to investigate their apoptotic activity. The obtained results revealed that they induced cell-cycle arrest in the G0-G1phase and reinforced apoptotic DNA fragmentation. Molecular modeling studies have been carried out to gain further understanding the binding mode of the target compounds together with field alignment to define the similar field properties.
S-glycosides in medicinal chemistry: Novel synthesis of cyanoethylene thioglycosides and their pyrazole derivatives
Elgemeie, Galal,Fathy, Nahed,Zaghary, Wafaa,Farag, Ayman
, p. 198 - 212 (2017/02/15)
A one-pot reaction of a sodium 2-cyanoethylene-1-thiolate salt with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides affords a new class of cyanoethylene thioglycosides. The conversion to the corresponding 5-aminopyrazoles confirms the E-co
TRICYCLIC PIPERAZINE DERIVATIVE
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Paragraph 0503, (2016/04/19)
Disclosed are compounds useful as inhibitors of Phosphodiesterase 1 (PDE1), compositions thereof, and methods of using the same.
A one-pot, three-component aminotriazine annulation onto 5-aminopyrazole-4-carbonitriles under microwave irradiation
Lim, Felicia Phei Lin,Luna, Giuseppe,Dolzhenko, Anton V.
, p. 521 - 524 (2015/02/19)
A one-pot, three-component, microwave-assisted reaction of 5-aminopyrazole-4-carbonitriles, triethyl orthoformate and cyanamide afforded novel 7-arylamino-substituted 4-aminopyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles. The reaction proceeded in a chemo- and regioselective manner resulting in the successful amino-1,3,5-triazine annulation onto 5-aminopyrazole-4-carbonitriles to give 4-aminopyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles. The operational simplicity of the method and high purity of the products, which can be isolated via simple filtration, make this approach attractive for the preparation of a library of compounds for drug discovery processes.
