5855-57-2Relevant articles and documents
Ru-NHC-Catalyzed Asymmetric Hydrogenation of 2-Quinolones to Chiral 3,4-Dihydro-2-Quinolones
Daniliuc, Constantin,Glorius, Frank,Hu, Tianjiao,Lückemeier, Lukas
, p. 23193 - 23196 (2021/09/25)
Direct enantioselective hydrogenation of unsaturated compounds to generate chiral three-dimensional motifs is one of the most straightforward and important approaches in synthetic chemistry. We realized the Ru(II)-NHC-catalyzed asymmetric hydrogenation of 2-quinolones under mild reaction conditions. Alkyl-, aryl- and halogen-substituted optically active dihydro-2-quinolones were obtained in high yields with moderate to excellent enantioselectivities. The reaction provides an efficient and atom-economic pathway to construct simple chiral 3,4-dihydro-2-quinolones. The desired products could be further reduced to tetrahydroquinolines and octahydroquinolones.
Palladium catalysed hydrolysis-free arylation of aliphatic nitriles for the synthesis of 4-arylquinolin-2-one/pyrazolone derivatives
Krishna Reddy, Singarajanahalli Mundarinti,Prasanna Kumari, Subramaniyan,Selva Ganesan, Subramaniapillai
, (2021/08/03)
Palladium catalysed addition of arylboronic acid to the readily available 2-cyano-(N-aryl)-acetamide or ethyl-2-cyanoacetate followed by subsequent reaction transform them into the biologically significant 4-arylquinolin-2-one or pyrazolone derivatives. The reaction conditions are robust enough to prevent the hydrolysis of ester/amide moiety during arylation. In addition, the unactivated nitrile moiety in the acetonitrile also converted to the corresponding acetophenone derivative.
Free energy perturbation guided Synthesis with Biological Evaluation of Substituted Quinoline derivatives as small molecule L858R/T790M/C797S mutant EGFR inhibitors targeting resistance in Non-Small Cell Lung Cancer (NSCLC)
Azad, Rajaram,Karnik, Kshipra S.,Sarkate, Aniket P.,Tiwari, Shailee V.,Wakte, Pravin S.
, (2021/08/09)
Two different schemes of novel substituted quinoline derivatives were designed and synthesized via simple reaction steps and conditions. A comparative molecular docking study was carried out on two different types of EGFR enzymes which include wild-type (PDB: 4I23) and T790M mutated (PDB: 2JIV) respectively. Compounds were also validated upon T790M/C797S mutated (PDB ID: 5D41) EGFR enzyme at the allosteric binding site. Free energy perturbations were carried out to determine the absolute binding free energy of a protein–ligand complex in the form of ΔGbinding, which in turn provided 4ab and 5ad as the most potential contenders through the structural enhancement in the determined initial scaffolds. Anticancer activity of the synthesized derivatives was examined against HCC827, H1975 (L858R/T790M), A549, and HT-29 cell lines by standard MTT assay. Compound 4ad (6-chloro-2-(isoindolin-2-yl)-4-methylquinoline) has shown excellent inhibitory activities against mutant EGFR kinase with IC50 value 0.91 μM. The potency of compounds 4ab, 4ad and 5ad was compared through an insilico ADMET study.
