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.).
Computational and Synthetic approach with Biological Evaluation of Substituted Quinoline derivatives as small molecule L858R/T790M/C797S triple mutant EGFR inhibitors targeting resistance in Non-Small Cell Lung Cancer (NSCLC)
Karnik, Kshipra S.,Sarkate, Aniket P.,Tiwari, Shailee V.,Azad, Rajaram,Burra, Prasad V.L.S.,Wakte, Pravin S.
, (2021/02/05)
New substituted quinoline derivatives were designed and synthesized via a five-step modified Suzuki coupling reaction. 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. All docking studies confirmed high potency and flexibility towards wild type as well as a mutated enzyme. Anticancer activity of the synthesized derivatives was examined against HCC827, H1975 (L858R/T790M/C797S and L858R/T790M), A549, and HT-29 cell lines by standard MTT assay. Most of the quinoline derivatives revealed a significant cytotoxic effect. The IC50 values of 4-(4-methylquinolin-2-yl)phenyl 4-(chloromethyl)benzoate (5j) were found to be 0.0042 μM, 0.02 μM, 1.91 μM, 3.82 μM and 3.67 μM while IC50 values of osimertinib were 0.0040 μM, 0.02 μM, ND, 0.99 μM and 1.22 μM, respectively. Compound 5j has shown excellent inhibitory activities against EGFR kinases triple mutant with IC 50 value 1.91 μM. It was observed that, compared to H1975, A549 and A431 cell lines, synthesized compounds significantly inhibited proliferation of the HCC827 cell line. These data suggested that synthesized compounds showed promising selective anticancer activity against tumor cells harboring EGFR Del E746-A750. The potency of compound 5j was compared through molecular dynamic simulations and an insilico ADMET study. QSAR models were generated and the best model was correctly compared with respect to predicted and observed activity of compounds. The built model will assist to design, refine and construct novel substituted quinoline derivatives as potent EGFR inhibitors in near future.
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.
Computational and experimental evaluation of α-(N-2-quinolonyl)ketones: a new class of nonbiaryl atropisomers
Bootsma, Andrea N.,Anderson, Carolyn E.
, p. 4834 - 4837 (2016/10/05)
Given the usefulness of atropisomers within both asymmetric catalysis and pharmaceuticals, a thorough computational study of substituted α-(N-2-quinolonyl)ketones has been conducted. This class of tertiary amides is unique, as the amide is embedded within an aromatic construct, and the nitrogen bears an aliphatic substituent. Using a computational approach, 8′-substituted quinolones were identified as potential class 2 and 3 atropisomeric targets with calculated C–N rotational barriers of greater than 20?kcal/mol. These results, along with experimental efforts toward the synthesis of these targets, are reported.
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.
Pyridine and related aza heterocycle derivatives as cardiovascular agents
-
, (2008/06/13)
Novel pharmaceutical compounds and compositions having nitrogen containing ring systems which may be represented by the following structural formula: wherein R1 or R3 is a moiety of the formula: wherein R6 is selected from either hydrogen or acetyl; R7 is selected from 2, 3 or 4-pyridyl or 1-imidazolyl and Q is -(CH2)n, where n is an integer from 1 to 5 and R1 and R2, R2 and R3, R3 and R4 or R4 and R5 taken together may be -CH=CH-CH=CH-. The compounds and compositions are useful as inhibitors of thromboxane synthetase and in the treatment of hypertension and arrythmia in mammals.
