Progress in the Chemistry of Tetrahydroquinolines

Muthukrishnan, Isravel; Sridharan, Vellaisamy; Menéndez, J. Carlos

doi:10.1021/acs.chemrev.8b00567

Cited by 349 publications

(200 citation statements)

References 697 publications

(935 reference statements)

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“…In contrast, the microwave procedure showed the highest products yields (67-72%) within 30 min of reaction at 160 • C. As a second reaction step, the microwave methodology allowed us to produce the propargyl derivatives in an efficient and environmentally friendly approach. The reaction conditions optimization involved the modification of the heating source [90,91]. The reaction conditions optimization involved the modification of the heating source [90,91].…”

Section: Synthesis Of N-propargylanilinesmentioning

confidence: 99%

“…The reaction conditions optimization involved the modification of the heating source [90,91]. The reaction conditions optimization involved the modification of the heating source [90,91]. Thus, the total reaction time was reduced from 96 h to 15 min (Table 4) through microwave-assisted methodology and compound yields were 2.5-fold increase in comparison with conventional procedures.…”

Section: Synthesis Of N-propargylanilinesmentioning

confidence: 99%

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Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

et al. 2020

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The coagulation cascade is the process of the conversion of soluble fibrinogen to insoluble fibrin that terminates in production of a clot. Factor Xa (FXa) is a serine protease involved in the blood coagulation cascade. Moreover, FXa plays a vital role in the enzymatic sequence which ends with the thrombus production. Thrombosis is a common causal pathology for three widespread cardiovascular syndromes: acute coronary syndrome (ACS), venous thromboembolism (VTE), and strokes. In this research a series of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives as a potential factor Xa (FXa) inhibitor were designed, synthesized, and evaluated for their FXa inhibitor activity, cytotoxicity activity and coagulation parameters. Rational design for the desired novel molecules was performed through protein-ligand complexes selection and ligand clustering. The microwave-assisted synthetic strategy of selected compounds was carried out by using Ullmann-Goldberg, N-propargylation, Mannich addition, Friedel-Crafts, and 1,3-dipolar cycloaddition type reactions under microwave irradiation. The microwave methodology proved to be an efficient way to obtain all novel compounds in high yields (73–93%). Furthermore, a thermochemical analysis, optimization and reactivity indexes such as electronic chemical potential (µ), chemical hardness (η), and electrophilicity (ω) were performed to understand the relationship between the structure and the energetic behavior of all the series. Then, in vitro analysis showed that compounds 27, 29–31, and 34 exhibited inhibitory activity against FXa and the corresponding half maximal inhibitory concentration (IC50) values were calculated. Next, a cell viability assay in HEK293 and HepG2 cell lines, and coagulation parameters (anti FXa, Prothrombin time (PT), activated Partial Thromboplastin Time (aPTT)) of the most active novel molecules were performed to determine the corresponding cytotoxicity and possible action on clotting pathways. The obtained results suggest that compounds 27 and 29 inhibited FXa targeting through coagulation factors in the intrinsic and extrinsic pathways. However, compound 34 may target coagulation FXa mainly by the extrinsic and common pathway. Interestingly, the most active compounds in relation to the inhibition activity against FXa and coagulation parameters did not show toxicity at the performed coagulation assay concentrations. Finally, docking studies confirmed the preferential binding mode of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives inside the active site of FXa.

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Section: Synthesis Of N-propargylanilinesmentioning

confidence: 99%

Section: Synthesis Of N-propargylanilinesmentioning

confidence: 99%

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

et al. 2020

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“…[10] The initially formed 1,3-bis-borylated tetrahydroquinolines were converted to the 3-hydroxytetrahydroquinolines upon the one-pot oxidation with sodium perborate tetrahydrate. Quinolines with alkyl, aryl, or halide groups at the C5 to C8 positions were found to display minimal impact on the formation of the desired β-borylated products (2)(3)(4)(5)(6)(7)(8)(9)(10). An ethereal sp 2 CÀ O bond (aryloxy group) was tolerated under the present reductive conditions to give the product 11 in 79% yield.…”

mentioning

confidence: 99%

“…[1] As a result, there have been considerable interests in the development of efficient and selective catalytic routes to tetrahydroquinolines and their derivatives. [2] Hydrogenation of quinolines is undoubtedly the most straightforward and atom-economic approach to access tetrahydroquinolines. [3] However, this procedure often leads to exhaustively reduced products with inferior functional group tolerance, thus limiting the resultant molecular diversity in the reduced N-heterocyclic products to serve as a synthetic intermediate.…”

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confidence: 99%

Double Hydroboration of Quinolines via Borane Catalysis: Diastereoselective One Pot Synthesis of 3‐Hydroxytetrahydroquinolines

et al. 2019

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Described herein is an organoboranecatalysed consecutive borylative reduction of quinolines and isoquinolines to furnish tetrahydro(iso) quinolines bearing a C(sp 3 )À B bond β to the nitrogen atom. The installed CÀ B bond is oxidatively transformed to the hydroxy group in one pot. The present double hydroboration is proposed to proceed via a stepwise ionic mechanism involving a boronium ion. The stereo-outcome was found to be dependent on the position (C2 vs C4) of the substituents in quinolines.

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“…[4] Therefore,the construction of quinoline compounds has received considerable attention. [5,6] Thed evelopment of efficient and stereoselective methods for quick access to chiral quinoline derivatives is of significant value. N-heterocyclic carbene (NHC) organic catalysis offers versatile reaction modes in asymmetric synthesis.…”

mentioning

confidence: 99%

NHC‐Catalyzed Chemoselective Reactions of Enals and Aminobenzaldehydes for Access to Chiral Dihydroquinolines

Liu

Luo

et al. 2019

Angew Chem Int Ed

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An N‐heterocyclic carbene (NHC)‐catalyzed reaction between α‐bromoenals and 2‐aminoaldehydes has been developed. Key steps include chemoselective reaction of the NHC catalyst with one of the aldehyde substrates (the bromoenal) to eventually generate an α,β‐unsaturated acylazolium intermediate. Addition of the nitrogen atom of aminoaldehyde to the unsaturated azolium ester intermediate followed by intramolecular aldol reaction, β‐lactone formation, and decarboxylation leads to chiral dihydroquinolines with high optical purity. The dihydroquinoline products, which are quickly prepared by using this method, can be readily transformed into a diverse set of functional molecules such as pyridines and chiral piperidines.

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Progress in the Chemistry of Tetrahydroquinolines

Cited by 349 publications

References 697 publications

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

Double Hydroboration of Quinolines via Borane Catalysis: Diastereoselective One Pot Synthesis of 3‐Hydroxytetrahydroquinolines

NHC‐Catalyzed Chemoselective Reactions of Enals and Aminobenzaldehydes for Access to Chiral Dihydroquinolines

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