66859-09-4

Upstream product

• 16502-01-5 tetrahydrobetacarboline 
• 98-88-4 benzoyl chloride 
• 80029-43-2 1-hydroxybenzotriazol-hydrate 
• 65-85-0 benzoic acid 
• 61-54-1 tryptamine 
• 120-72-9 indole 
• 487-89-8 Indole-3-carboxaldehyde 
• 3156-51-2 3-(2-nitroethenyl)-1H-indole 
• 6502-82-5 N_b-formyltryptamine 
• 4894-26-2 3,4-dihydro-β-carboline 

Downstream Products

• 98263-41-3 2-Benzamido-4-oxo-1,2,3,4-tetrahydro β-carboline 
• 47064-53-9 2,3,4,9-Tetrahydro-2-(2-phenylmethyl)-1H-pyrido<3,4-b>indole 

Relevant academic research and scientific papers

Catalytic Enantioselective Synthesis of Spirooxindoles by Oxidative Rearrangement of Indoles

Oxidative rearrangement of indoles to access oxindoles has been used as a key step in complex molecule synthesis. We report a catalytic enantioselective variant of this transformation by chiral phosphoric acid catalysis, providing rapid access to a range of enantioenriched spirooxindoles. The high enantioselectivity is controlled by dynamic kinetic resolution.

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.

Discovery of tetrahydro-?-carboline derivatives as a new class of phosphodiesterase 4 inhibitors

Abstract: Phosphodiesterase 4 is the primary enzyme responsible for degradation of the second messenger cAMP in many of the cells releasing proinflammatory mediators. Inhibition of this enzyme could help in the management of various inflammatory conditions such as asthma, chronic obstructive pulmonary disorder, arthritis, and psoriasis. In this study, two novel series of tetrahydro-β-carbolines were designed by combining the pharmacophoric features of both tadalafil and piclamilast. Twenty-two compounds were synthesized and assessed for Phosphodiesterase 4 inhibition, four of them showed superior activity to the reference compound IBMX. Docking studies showed that the prepared compounds interact with the crucial Gln443 with variable interactions with the hydrophobic pocket Q2. This is the first report of tetrahydro-β-carbolines as a scaffold for Phosphodiesterase 4 inhibition. Currently, further optimization of the substituents is carried out to fine-tune the hydrophobic interactions and enhance the potency of this novel series of inhibitors.

7-aniline benzopyridine compound as well as preparation method and application thereof

The invention discloses a 7-aniline benzopyridine derivative and a preparation method thereof. The 7-aniline benzopyridine derivative has the following structural general formula shown in the description, wherein R1 is an arbitrary substituted acyl group, and R2 is an arbitrary substituted phenyl group. The preparation method comprises the following steps: adopting tricyclic pyrido indole as a starting material, carrying out photocatalytic oxidation reaction with a photosensitizer to obtain a more stable peroxide, and finally carrying out reaction on the peroxide and substituted aniline under the action of trifluoroacetic acid to obtain the 7-aniline benzopyridine derivative as a target product. The compound can be used for being developed into a drug for treating a breast cancer, a lung cancer, a liver cancer, a cervical cancer, a prostate cancer and the like.

Synthesis and biological evaluation of novel tetrahydro-β-carboline derivatives as antitumor growth and metastasis agents through inhibiting the transforming growth factor-β signaling pathway

The transforming growth factor beta (TGFβ) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGFβ signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-β-carboline derivatives from virtual screening which potentially inhibit the TGFβ signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-β- carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGFβ signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.

Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin

We present the design, synthesis, and biological activity of three classes of tryptamine derivatives, which are non-planar analogues of the toxic anti-cancer agent fascaplysin. We show these compounds to be selective inhibitors of CDK4 over CDK2, the most active compound 9q has an IC50 for the inhibition of CDK4 of 6 M. The Royal Society of Chemistry 2006.

Antibacterial compounds

Compounds of the formula (I) are disclosed which are FabI inhibitors and are useful in the treatment bacterial infections: wherein: R1is Ar or Het; R2is H, C1-6alkyl or Ar—C0-6alkyl; X is H, C1-4alkyl

Preparation of vincadifformine and related derivatives

This invention relates to the preparation of vincadifformine and related derivatives which are useful as starting material for the synthesis of among other alkaloids vincamine and other similar compounds possessing interesting psychopharmacologic properti

Preparation of vincadifformine

The invention relates to the preparation of vincadifformine. Tetrahydro-β-carboline (II) is reacted with benzoyl chloride to provide 2-benzoyl-1,2,3,4-tetrahydro-9H-pyrido-[3,4b]-indole (III). Then compound (III) is reduced to give 2-benzyl-1,2,3,4-tetrahydro-9H-pyrido[3,4b]-indole (IV). Thereafter, compound (IV) is transformed by t-butyl hypochlorite into chloroindolenine derivative (V) which is immediately treated with thallium t-butyl methyl malonate to give t-butyl methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino-[4,5b]-indole-5,5-dicarboxylate (VI). Compound (VI) is then partly decarboxylated into methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino-[4,5b]-indole-5-carboxylate (VII). Compound (VII) is hydrogenated to give methyl 1,2,3,4,5,6-hexahydroazepino-[4,5b]-indole-5-carboxylate (IX). In an alternative embodiment, compound (VI) can be hydrogenated to methyl t-butyl 1,2,3,4,5,6-hexahydroazepino-[4,5b]-indole-5,5-dicarboxylate (VIII) which is then decarboxylated into compound (IX). Compound (IX) is condensed with 1-bromo-4-formyl-hexane to yield vincadifformine (I).