59856-27-8Relevant academic research and scientific papers
Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening
Chatterjee, Arindam,Cutler, Stephen J.,Doerksen, Robert J.,Khan, Ikhlas A.,Williamson, John S.
, p. 6409 - 6421 (2014)
Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2-c]quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP non-competitive CDK5/p25 inhibitors with good CDK2/E selectivity.
Thiophene quinolone compound as well as preparation method and application thereof
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, (2021/09/26)
The invention belongs to the field of medicines, and particularly relates to a thiophene quinolone compound as well as a preparation method and application thereof. The structural formula of the thiophene quinolone compound disclosed by the invention is shown I. The thiophene quinolone compound shown in the formula I is obtained, CDK5 inhibition activity is high, and water solubility is good.
Method for synthesizing bactericide intermediate
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Paragraph 0006, (2020/01/12)
The invention discloses a method for synthesizing a bactericide intermediate. The method comprises the following steps: adding diethyl malonate into a certain amount of aniline for ammonolysis, addingN1,N3-diphenyl malonamide obtained after ammonolysis into polyphosphoric acid for cyclization, carrying out refining after the reaction is completed to obtain 4-hydroxyquinolin-2(1H)-one, performingan amine methylation reaction to obtain 3-[(phenylamino)methylene]-quinoline-2,4(1H,3H)-dione, performing chlorination hydrolysis on the 3-[(phenylamino)methylene]-quinoline-2,4(1H,3H)-dione to obtaina crude product, and carrying out pulping by toluene to obtain the bactericide intermediate. The method provided by the invention has the advantages of easily available raw materials, low cost, simple operation and high yield, and is suitable for industrial production.
Synthesis and antitumor activity of novel amsacrine analogs: The critical role of the acridine moiety in determining their biological activity
Chilin, Adriana,Marzaro, Giovanni,Marzano, Christine,Via, Lisa Dalla,Ferlin, Maria Grazia,Pastorini, Giovanni,Guiotto, Adriano
experimental part, p. 523 - 529 (2009/06/20)
A new series of N-[4-(2′-oxo-2H-pyrano[2,3-b]quinolin-5′-ylamino)-phenyl]-methanesulfonamides was prepared and analyzed as novel amsacrine-like derivatives. Our preliminary biological evaluation has shown that the replacement of the acridine moiety with t
Nucleophilic Chlorination of 3-Formyl-4-hydroxy-quinolin-2(1H)-ones
Fiala, Werner,Stadlbauer, Wolfgang
, p. 128 - 134 (2007/10/02)
Chlorination of 1-substituted 3-formyl-4-hydroxy-2-quinolones (1a, b) with phosphorylchloride leads to 4-chloro-3-dichloromethylquinolones (2), which can be hydrolyzed to 4-chloro-3-formylquinolones (4).From the anilinomethylene quinolinediones (3), at lo
