6650-04-0

Usage

Uses

Used in Pharmaceutical Industry:
2,3,4,9-Tetrahydro-1-isopropyl-1H-pyrido[3,4-b]indole is used as a starting material for the synthesis of new drugs. Its unique molecular structure and potential biological activity make it a promising candidate for the development of novel therapeutic agents.
Used in Research Applications:
2,3,4,9-Tetrahydro-1-isopropyl-1H-pyrido[3,4-b]indole is used as a research tool for studying the mechanisms of action of psychoactive substances. Its potential to interact with neurotransmitter receptors in the brain makes it of interest for understanding the effects of psychoactive drugs and for the development of new psychoactive drugs.

InChI:InChI=1/C14H18N2/c1-9(2)13-14-11(7-8-15-13)10-5-3-4-6-12(10)16-14/h3-6,9,13,15-16H,7-8H2,1-2H3

Upstream product

• 61-54-1 tryptamine 
• 78-84-2 isobutyraldehyde 
• 146560-30-7 C₁₄H₁₈N₂ 
• 65601-08-3 1-isopropyl-4,9-dihydro-3H-pyrido[3,4-b]indole 
• 343-94-2 tryptamine hydochloride 

Downstream Products

• 903437-40-1 1-isopropyl-2-tosyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole 
• 22314-95-0 1-isopropyl-9H- pyrido[3,4-b]indole 
• 335094-05-8 (1-isopropyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)(phenyl)methanone 

Relevant academic research and scientific papers

Discovery of novel liver X receptor inverse agonists as lipogenesis inhibitors

Based on the co-crystal structures of LXRβ and its agonists (spiro [pyrrolidine-3,3′-oxindole] derivatives) discovered by us previously, we designed and synthesized a compound library to explore the agonistic activities. The library was screened with luciferase reporter assays, interestingly, it resulted in the discovery of 10 LXR inverse agonists besides 5 LXR agonists. To clarify the mechanism of the actions, we conducted molecular dynamics (MD) simulations on the LXR and inverse agonists complexes, and revealed that H3, H11 and H12 configurations are the key to turn on agonism or inverse agonism status for LXR. Binding tightly with H3, pushing H11 out and destabilizing H12 could form a bigger hydrophobic groove to accommodate NCOR1 to turn on LXR inverse agonism. The inverse agonist 10rr was further studied, and found as a lipogenesis inhibitor through down-regulating LXR target genes SREBP-1c, ACC, FAS and SCD-1, and demonstrated lipid-lowering effects in 3T3-L1 cells, HepG2 cells and mice with Triton WR-1339-induced hyperlipidemia. Therefore, we have proved that LXR inverse agonists can be promising agents for hyperlipidemia treatment.

Structural simplification of evodiamine: Discovery of novel tetrahydro-β-carboline derivatives as potent antitumor agents

Natural products (NPs) have played a crucial role in the discovery and development of antitumor drugs. However, the high structural complexity of NPs generally results in unfavorable physicochemical profiles and poor drug-likeness. A powerful strategy to tackle this obstacle is the structural simplification of NPs by truncating nonessential structures. Herein, a series of tetrahydro-β-carboline derivatives were designed by elimination of the D ring of NP evodiamine. Structure-activity relationship studies led to the discovery of compound 45, which displayed highly potent antitumor activity against all the tested cancer cell lines and excellent in vivo antitumor activity in the HCT116 xenograft model with low toxicity. Further mechanistic research indicated that compound 45 acted by dual Top1/2 inhibition and induced caspase-dependent cell apoptosis coupled with G2/M cell cycle arrest. This proof-of-concept study validated the effectiveness of structural simplification in NP-based drug development, discovered compound 45 as a potent antitumor lead compound and enriched the structure–activity relationships of evodiamine.

TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: Facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline

Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.

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.

Spiro (3,3'-isopropylpyrrolidineoxoindole) liver X receptor regulator and preparation method and application thereof

The invention relates to a spiro (3,3'-isopropyl pyrrolidineoxoindole) liver X receptor modifier and a preparation method and application thereof, particularly provides a compound which is a compoundshown in a formula (I), or a stereoisomer, a geometric i

Catalytic Oxidative Coupling Cyclization for Construction of Benzofuroindolenines under Mild Reaction Conditions

We describe iron-catalyzed oxidative coupling cyclization of tetrahydrocarbazoles or THβCs or THγCs to form benzofuroindolenines as fused polycyclic indoles. This mild, efficient and simple approach afforded a library of more than 52 complex compounds across a range of substrate classes with good to excellent yields. (Figure presented.).

Metal free one pot synthesis of Β-carbolines via a domino Pictet-Spengler reaction and aromatization

A convenient and efficient metal free, atom economical flexible synthesis of β-carbolines involving a domino Pictet-Spengler reaction and aromatization in oxygen atmosphere in N-methyl-2-pyrollidone (NMP) is described. Variety of aryl, heteroaryl and aliphatic aldehydes were found to be good substrates for this methodology. Several β-carbolines (6a-6t) and β-carboline methyl esters (7a-7e) were synthesized using this methodology.The same reaction carried out in argon atmosphere in the presence of catalytic amount of acid in NMP furnished, tetrahydro-β-carbolines (4a-4g).

Candida antarctica lipase B catalysed kinetic resolution of 1,2,3,4-tetrahydro-?-carbolines: Substrate specificity

In the frame of substrate specificity, CAL-B-catalysed asymmetric N-alkoxycarbonylations of 1-substituted tetrahydro-?-carbolines (Me, Et, Pr, iPr) have been studied. High enantioselectivities (>200) were observed, when alkoxycarbonylation of racemic compounds (±)-1,3,5,7 were performed in DIPE in the presence of phenyl allyl carbonate and Et3N at 60 °C using ultrasound shaking method. The reaction time increased considerably with increasing substituent size on C1; however, the isopropyl-substituted compound proved to be too bulky for the optimum activity of CAL-B. The (R)-carbamate enantiomers were hydrolysed using Pd2(dba)3.CHCl3 and the enantiomers of the free amines were obtained with excellent ee (>99%).

An acid-free Pictet-Spengler reaction using deep eutectic solvents (DES)

Deep eutectic solvents (such as the combination of either urea or glycerol with choline chloride) are effective solvents/organocatalysts for Pictet-Spengler condensations to form carbolines. The reaction conditions are quite mild and do not require additi

Simple and efficient synthesis of tetrahydro-β-carbolines via the Pictet-Spengler reaction in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)

1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) can act as both the solvent and the catalyst to promote the Pictet-Spengler reactions between tryptamine derivatives and aldehydes or activated ketones. For most substrates, removing the low boiling point HFIP by distillation directly afforded tetrahydro-β-carbolines in high yields.