6649-95-2

Usage

Molecular Structure

A complex structure consisting of a pyridoindole core with a 2,3,4,9-tetrahydro substitution and a methoxyphenyl group attached at position 1.

Usage

Commonly used in organic synthesis and pharmaceutical research.

Biological Activities

Exhibits a range of biological activities.

Potential

Serves as a drug candidate or a precursor in the synthesis of other biologically active compounds.

Importance

Its properties and reactivity make it of interest for further investigation in the fields of medicinal chemistry and drug discovery.

Upstream product

• 343-94-2 tryptamine hydochloride 
• 591-31-1 3-methoxy-benzaldehyde 
• 61-54-1 tryptamine 
• 1711-05-3 m-anisoyl chloride 
• 339165-45-6 C₁₈H₁₈N₂O₂ 
• 939386-73-9 1-(3-methoxyphenyl)-4,9-dihydro-3H-pyrido[3,4-b]indole 

Downstream Products

• 1112426-46-6 C₂₅H₂₄N₂O₃S 
• 95813-31-3 1-(3-methoxyphenyl)-9H-pyrido[3,4-b]indole 
• 1620753-99-2 2-ethyl-1-(3-methoxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline 
• 1620754-15-5 dimethyl 3-ethyl-6-(3-methoxyphenyl)-2,3,6,7-tetrahydro-1H-azocino[5,4-b]indole-4,5-dicarboxylate 
• 1620754-11-1 1-[3-ethyl-6-(3-methoxyphenyl)-2,3,6,7-tetrahydro-1H-azocino[5,4-b]indol-5-yl]ethanone 

Relevant academic research and scientific papers

Asymmetric Biocatalytic Synthesis of 1-Aryltetrahydro-β-carbolines Enabled by “Substrate Walking”

Stereoselective catalysts for the Pictet–Spengler reaction of tryptamines and aldehydes may allow a simple and fast approach to chiral 1-substituted tetrahydro-β-carbolines. Although biocatalysts have previously been employed for the Pictet–Spengler react

Organic base-promoted efficient dehydrogenative/decarboxylative aromatization of tetrahydro-β-carbolines into β-carbolines under air

Organic base DBN has been identified as an efficient reagent for promoting the dehydrogenative/decarboxylative aromatization of tetrahydro-β-carbolines under air atmosphere, to access the corresponding β-carbolines in moderate to good yields. The utility of this protocol for the gram-scale synthesis of β-carboline alkaloids eudistomin U (7) and harmane (10) has also been demonstrated.

Iodine-Catalyzed Metal-Free Oxidative Ring Opening of 1-Aryltetrahydro-β-carbolines: Facile Synthesis of C-2 Aroyl and Aryl Methanimino Indole Derivatives

Indole derivatives bearing C-2 substituents have garnered a lot of attention due to their diverse biological activities. Various methods forthe synthesis of these compounds have been reported. Inspired by the hydrolysis of imines, an oxidative ring-opening reaction of 1-aryltetrahydro-β-carbolines with catalytic iodine in aqueous hydrogen peroxide, and also in the presence of appropriate amines, is described for the generation of 2-aroyl and arylmethanimine indole derivatives. The reaction proceeds under mild reaction conditions with ethanol as the solvent or under solvent-free conditions, respectively. This metal-free strategy facilitates the formation of the desired substituted C-2 indoles in moderate to excellent yields. The utility of this reaction is demonstrated by a facile multigram-scale synthesis of Luzindole, a selective melatonin receptor antagonist and an investigational drug against depression and disruption of the circadian rhythm.

Design, synthesis and biological evaluation of a novel library of antimitotic C2-aroyl/arylimino tryptamine derivatives that are also potent inhibitors of indoleamine-2, 3-dioxygenase (IDO)

A novel library of C2-substituted tryptamines (based on diverse C2-aroyl/arylimino indoles and indole-diketopiperazine hybrids) possessing antimitotic properties were designed, synthesized and screened for their inhibitory activity against tubulin polymerization, and against proliferation of A549 lung cancer, HeLa cervical cancer, MCF7 breast cancer and HePG2 liver cancer cell lines. The design of molecules were inspired from known antimitotic compounds and natural products. The molecular docking of the designed compounds indicated that they bind to the colchicin binding site of tubulin. They were synthesized by a unique iodine catalysed oxidative ring opening reaction of 1-aryltetrahydro-β-carbolines. Among the compounds synthesized quite a few compounds induced cytotoxicity on the cancer cells by disrupting the tubulin polymerization. They were found to be non-toxic for healthy cells. Immuno Fluorescence study for the most active molecules (between ~6 μM concentration) against A549 and HeLa cells demonstrated complete disruption and shrinkage of the microtubule structures. These compounds also inhibited indoleamine-2, 3-dioxygenase with low micromolar IC50.

Synthesis and Investigation of Tetrahydro-β-carboline Derivatives as Inhibitors of the Breast Cancer Resistance Protein (ABCG2)

The breast cancer resistance protein (ABCG2) transports chemotherapeutic drugs out of cells, which makes it a major player in mediating multidrug resistance (MDR) of cancer cells. To overcome this mechanism, inhibitors of ABCG2 can be used. Only a few potent and selective ABCG2 inhibitors have been discovered, i.e., fumitremorgin C (FTC), Ko143, and the alkaloid harmine, which contain a tetrahydro-β-carboline or β-carboline backbone, respectively. However, toxicity and or instability prevent their use in vivo. Therefore, there is a need for further potent inhibitors. We synthesized and pharmacologically investigated 37 tetrahydro-β-carboline derivatives. The inhibitory activity of two compounds (51, 52) is comparable to that of Ko143, and they are selective for ABCG2 over ABCB1. Furthermore, they are able to reverse the ABCG2-mediated resistance toward SN-38 and inhibit the ATPase activity. The cytotoxicity data show that their inhibitory effect is substantially higher than their toxicity.

N-Bromo-succinimide promoted synthesis of β-carbolines and 3,4-dihydro-β-carbolines from tetrahydro-β-carbolines

Herein, we report a facile synthesis of 3,4-dihydro-β-carbolines and aromatic β-carbolines from tetrahydro-β-carbolines, mediated by N-bromosuccinimide in toluene at 0°C to room temperature (rt), in good to moderate yields.

A facile and efficient synthesis of tetrahydro-β-carbolines

This Letter describes a convenient, efficient, and clean synthesis of various tetrahydro-β-carbolines catalyzed by propane phosphonic acid anhydride T3P under microwave irradiation.

Synthetic analogs of indole-containing natural products as inhibitors of sortase A and isocitrate lyase

Guided by the inhibitory activities of indole-containing natural products against isocitrate lyase (ICL) from Candida albicans and sortase A (SrtA) from Staphylococcus aureus, a series of compounds structurally analogous to natural products were synthesized. Eight SrtA inhibitors and an ICL inhibitor having higher activities than the natural products were discovered by screening the enzyme inhibitory activities of synthesized compounds. Among the SrtA inhibitors discovered, six exhibited higher activities than p-hydroxymercuribenzoic acid, which suggests that these compounds have great potential as alternative antibacterial agents.

A mild and efficient route to 2-benzyl tryptamine derivatives via ring-opening of β-carbolines

We described a mild and easy method, in two steps, by which various benzyl groups were introduced in the C-2 position of tryptamine. The first step consisted on the synthesis of β-carbolines, starting from tryptamine derivatives, by a Pictet-Spengler reaction. Ring-opening of the β-carbolines, by hydrogenation, led to the desired 2-substituted benzyl tryptamine indole products. A supplementary step of alkylation could be realized to give N-alkyl-2-substituted benzyl tryptamine. During these reactions, nitrogen atoms require no step of protection.

M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: Serominic compounds

Chronic low-dose treatment of rats with the psychomimetic drug, phencyclidine, induces regionally specific metabolic and neurochemical changes in the CNS that mirror those observed in the brains of schizophrenic patients. Recent evidence suggests that drugs targeting serotoninergic and muscarinic receptors, and in particular 5-HT7 antagonists and M4 agonists, exert beneficial effects in this model of schizophrenia. Compounds that display this combined pattern of activity we refer to as serominic compounds. Based upon leads from natural product screening, we have designed and synthesised such serominic compounds, which are principally arylamidine derivatives of tetrahydroisoquinolines, and shown that they have the required serominic profile in ligand binding assays and show potential antipsychotic activity in functional assays.