3913-17-5Relevant articles and documents
Cp*Rh(III)-Catalyzed Directed C?H Methylation and Arylation of Quinoline N-Oxides at the C-8 Position
Wang, Bao,Li, Chunpu,Liu, Hong
, p. 3029 - 3034 (2017)
Herein, we report a Cp*Rh(III)-catalyzed directed C?H methylation of quinoline N-oxides at the C-8 position using commercially available organotrifluoroborates as reagents. This method features perfect regioselectivity, relatively mild reaction conditions, and diverse functional group tolerance with good to excellent yields. Additionally, direct C-8 arylated quinoline N-oxides products could also be obtained under the same conditions. Preliminary mechanistic experiments were conducted and a possible mechanism was proposed. (Figure presented.).
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.
Diastereoselective hydrogenation of substituted quinolines to enantiomerically pure decahydroquinolines
Heitbaum, Maja,Froehlich, Roland,Glorius, Frank
supporting information; experimental part, p. 357 - 362 (2010/05/19)
The stereoselective hydrogenation of auxiliary-substituted quinolines was used to build up saturated and partially saturated heterocycles. In a first step, the formation and diastereoselective hydrogenation of 2-oxazolidinone- substituted quinolines to 5,6,7,8-tetrahydroquinolines is reported. In this unprecedented process, stereocenters on the carbocyclic quinoline ring were formed with a dr of up to 89:11. Platinum oxide as a catalyst and trifluoroacetic acid as a solvent were found to be optimal for high levels of chemo- and stereoselectivity in this step. In a second hydrogenation step, the completely saturated decahydroquinolines with 4 newly formed stereocenters were obtained with enantioselectivities of up to 99%. Rhodium on carbon as a catalyst and acetic acid as a solvent gave the best results for this hydrogenation and allowed a traceless cleavage of the chiral auxiliary. Thus, this new method allows an efficient stereoselective synthesis of valuable 5,6,7,8-tetrahydro- and decahydroquinoline products.
