A Facile Synthesis of 3-Substituted 9H-Pyrido[3,4-b]indol-1(2H)-one Derivatives from 3-Substituted β-Carbolines

Lin, Guowu; Wang, Yue; Zhou, Qingfa; Tang, Weifang; Wang, Jian; Lü, Tao

doi:10.3390/molecules15085680

Cited by 18 publications

(20 citation statements)

References 27 publications

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“…24,25) And the treatment of 1a with excess thionyl chloride in anhydrous EtOH at reflux for 6 h gave ethyl 1,2,3,4-tetrahydro-β-carboline-1-carboxylate (1b) as a white solid. 26) Then, ethyl β-carboline-1-carboxylate (1c) was carried out by dehydrogenation with KMnO 4 in N,Ndimethylformamide (DMF) at room temperature for 24 h. 27) 1-Amino-β-carboline (1d) was prepared by the aminolysis of (1c).…”

Section: Methodsmentioning

confidence: 99%

“…mp 321-323°C (MeOH 6-Aminosulfonyl-1-carbamoyl-3-methoxy-β-carboline (3) For compound 3, the same method with compound 4 as follow is used, only the cyclohexanol group was introduced from intermedium 3d. 27) Yield 57%. mp 165-167°C (MeOH).…”

Section: -Aminosulfonyl-1-carbamoyl-3-(1h-benzo[d]imidazol-2-yl)-β-cmentioning

confidence: 99%

“…24,25) And the treatment of 2a with excess thionyl chloride in anhydrous EtOH for 6 h at reflux gave ethyl 1,2,3,4-tetrahydro-β-carboline-3-carboxylate (2b) as a white solid in 88% yield. 27) Then, ethyl β-carboline-3-carboxylate (2c) was dehydrogenated with KMnO 4 in DMF at room temperature for 24 h.…”

Section: -Aminosulfonyl-1-carbamoyl-3-(1h-benzo[d]imidazol-2-yl)-β-cmentioning

confidence: 99%

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Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Wang

Jin

Lin

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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Series of 3-substituted of 6-aminosulfonyl-β-carbolines were designed and synthesized. In addition, the binding mode of these β-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular docking calculation. The results showed that replacement of 3-cyclohexylmethoxy group will increase the hydrophobic binding interaction with the deep hydrophobic pocket of CDK2 correlate to the higher binding intensity.Key words cyclin-dependent kinase 2; β-carboline; synthesis; molecular docking; fluorescence It is well known that the phases of the cell cycle are driven by cyclin-dependent kinases (CDKs). Upon complexation with its activating proteins, cyclin E or cyclin A, cyclin-dependent kinase 2 (CDK2) modulates the activity of many cellular substrates via phosphorylation on serine (Ser) and/or threonine (Thr) residues.1-4) Abnormal CDK control of the cell cycle has been strongly linked to the molecular pathology of cancer. 5)The importance of CDK2 for cell cycle progression has led to an active pursuit of small molecule inhibitors of this enzyme as a possible treatment against cancer and other hyper-proliferative disorders.6-9) All CDK inhibitors, identified so far, function by competing with ATP for binding to the catalytic site. Actually several CDK inhibitors have entered clinical evaluation for the treatment of cancer, including flavopiridol, amino-thiazole compound.10) In our program to develop CDK2 inhibitors, we recently investigate the β-carboline alkaloids containing a planar tricyclic system as a large group of naturally-occurring and synthetic alkaloids, [11][12][13][14] which has a broad spectrum of biochemical effects and pharmaceutical properties. These compounds have been shown to intercalate into DNA, to inhibit CDK, topisomerase and monoamine oxidase, and to interact with benzodiazepine receptors (BZ), 5-hydroxy serotonin receptors (5-HT), dopamine (DA) and imidazoline receptors. [15][16][17][18][19][20][21][22][23] Inspired by these results, our research group recently focused on first of all, using a structure-guided strategy based on CDK2 as appropriate means to generate potent CDK2 inhibitors; then to synthesize disubstituted β-carbolines and to complete their biological evaluation study. As a part of our systematic work, in this paper, structure modification of β-carboline based on increasing its hydrophobic nature has been adopted. Herein we reported the design and synthesis of series of 3-substituted of 6-aminosulfonyl-β-carbolines. Series of 3-substituted compounds with different hydrophobic groups (Chart 1) were synthesized and one of their structures was elucidated with X-ray crystal analysis. The new derivatives were prepared following the reaction sequences depicted in Charts 2-4. Their binding intensity with CDK2 was measured by fluorescence spectroscopy. ExperimentalSynthesis The target compounds were prepared using the reaction sequence. All the chemical structures of the synthesized compounds were confirmed by spectroscopic me...

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Section: Methodsmentioning

confidence: 99%

Section: -Aminosulfonyl-1-carbamoyl-3-(1h-benzo[d]imidazol-2-yl)-β-cmentioning

confidence: 99%

Section: -Aminosulfonyl-1-carbamoyl-3-(1h-benzo[d]imidazol-2-yl)-β-cmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Wang

Jin

Lin

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…[5] Oxidation reactions affording β-carbolin-1-ones were carried out in two-step fashion from 3-substituted β-carbolines, by oxidation with m-CPBA and treatment of the resulting N-oxides with acetic anhydride in a basic medium (Scheme 3). [6] The most common reduction reactions involving β-carbolines involve hydrogenation of 1,2-imine-type double bonds in dihydro-β-carbolines. Many natural products contain 1-substituted THBC units and so the synthesis of enantiomerically pure forms of these products has been an important synthetic challenge.…”

Section: Aromatizations and Reductions Of β-Carboline Systemsmentioning

confidence: 99%

“…[14] A group of dihydro-β-carboline derivatives were subjected to rhodium-catalysed asymmetric hydrogenation in the presence of chiral phosphorus ligands (Scheme 6). [15] An alternative to the above methods is an asymmetric reduction based on the supramolecular complex formed from calix [6]arene and a chiral amine as an enzyme mimetic and NaBH 4 as the reducing agent (Scheme 7). This elegant methodology, however, gives lower enantioselectivities than the previously described procedures.…”

Section: Aromatizations and Reductions Of β-Carboline Systemsmentioning

confidence: 99%

Chemistry of β‐Carbolines as Synthetic Intermediates

Domı́nguez

Pérez‐Castells

2011

Eur J Org Chem

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Abstractβ‐Carbolines are present in a wide variety of indole alkaloids that display important biological activities. Here we review the most recent aspects of the chemistry of β‐carbolines with a focus on functionalization of the β‐carboline system and transformations into other interesting compounds. Aromatizations, reductions and alkylations of the heterocyclic system are thus summarized first, followed by methodologies directed towards the formation of additional fused rings. Finally, rearrangements that transform β‐carbolines into other heterocyclic systems are covered.

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1(3)‐Formyl‐β‐carbolines: Potential Aldo‐X Precursors for the Synthesis of β‐Carboline‐Based Molecular Architectures

et al. 2017

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b-Carboline, ap rivileged scaffold in the alkaloid family,h as ab road spectrum of medicinal properties and is found in severalc ommercial drugs, such as tadalafil, cipargamin, anda becarnil. Owing to the immense pharmacological importance of b-carboline derivatives, their synthesis has been one of the frontier areas of research in recent years. In this context,1 (3)-formyl-9H-b-carbolines are promising "aldo-X" bifunctional building blocks (AXB3s) that offer alternate avenues for the diversity-oriented synthesis of b-carboline derivatives. This Focus Review is an assimilation of recent literature (2011)(2012)(2013)(2014)(2015)(2016)(2017) pertaining to the synthesis and applicationso f1 (3)-formyl-b-carbolines for the construction of b-carboline-tethered and -fused moleculara rchitectures. In addition, the medicinal potential of b-carboline derivatives has been highlighted.

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A Facile Synthesis of 3-Substituted 9H-Pyrido[3,4-b]indol-1(2H)-one Derivatives from 3-Substituted β-Carbolines

Cited by 18 publications

References 27 publications

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Synthesis and Structure of the β-Carboline Derivatives and Their Binding Intensity with Cyclin-Dependent Kinase 2

Chemistry of β‐Carbolines as Synthetic Intermediates

1(3)‐Formyl‐β‐carbolines: Potential Aldo‐X Precursors for the Synthesis of β‐Carboline‐Based Molecular Architectures

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