6208-43-1

Usage

InChI:InChI=1/C18H18N2/c1-2-6-14(7-3-1)12-20-11-10-18-16(13-20)15-8-4-5-9-17(15)19-18/h1-9,19H,10-13H2

Upstream product

• 3612-20-2 1-phenylmethyl-4-piperidone 
• 100-63-0 phenylhydrazine 
• 120656-71-5 N-(1-benzylpiperidin-4-ylidene)-N-(2-fluorophenyl)amine 
• 108-42-9 3-chloro-aniline 
• 1227476-15-4 Azobenzene 
• 100-39-0 benzyl bromide 
• 1346446-51-2 (1-benzylpiperidin-4-ylidene)-(3-chlorophenyl)amine 
• 129303-82-8 1-phenyl-1H-[1,2,3]triazolo[4,5-c]pyridine 
• 244-69-9 γ-carboline 
• 59-88-1 phenylhydrazine hydrochloride 

Downstream Products

• 1236142-54-3 5-benzoyl-2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole hydrochloride 
• 1354547-56-0 methyl 4-((2-benzyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 933978-56-4 C₁₄H₁₈N₂ 
• 1354547-51-5 tert-butyl 5-(4-(methoxycarbonyl)benzyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate 
• 1354547-52-6 methyl 4-((3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-53-7 methyl 4-((2-ethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-54-8 methyl 4-((2-isopropyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-55-9 methyl 4-((2-allyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-57-1 methyl 4-((2-(3-methoxybenzyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-58-2 methyl 4-((2-(4-methoxybenzyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-59-3 methyl 4-((2-(pyridin-4-ylmethyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-60-6 methyl 4-((2-(3-amino-3-oxopropyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-61-7 methyl 4-((2-(2-amino-2-oxoethyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 
• 1354547-62-8 methyl 4-((2-(4-amino-4-oxobutyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate 

Relevant academic research and scientific papers

Direct Synthesis of Indoles from Azoarenes and Ketones with Bis(neopentylglycolato)diboron Using 4,4′-Bipyridyl as an Organocatalyst

Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B2nep2) with a catalytic amount of 4,4′-bipyridyl under neutral reaction conditions, where 4,4′-bipyridyl acted as an organocatalyst to activate the B-B bond of B2nep2 and form N,N′-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of N,N′-diboryl-1,2-diarylhydrazines with ketones afforded N-vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3-substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N- and O-protecting functional groups.

Evaluation of γ-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors

Alzheimer's disease (AD) is the most common form of dementia. It is associated with the impairment of memory and other cognitive functions that are mainly caused by progressive defects in cholinergic and glutamatergic signaling in the central nervous system. Inhibitors of acetylcholinesterase (AChE) and ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) receptor family are currently approved as AD therapeutics. We previously showed using a cell-based assay of NMDA receptor-mediated glutamate-induced excitotoxicity that bis-γ-carbolinium conjugates are useful NMDA receptor blockers. However, these compounds also act as subnanomolar AChE inhibitors, which may cause serious anticholinergic side effects when applied in vivo. Here, we evaluated new structures containing γ-carbolines linked to phenothiazine via a propionyl spacer. These compounds were superior to the previously characterized bis-γ-carbolinium conjugates because they blocked NMDA receptors without requiring a quaternary pyridine N-atom and inhibited AChE with moderate IC50 values of 0.54–5.3 μM. In addition, these new compounds displayed considerable selectivity for the inhibition of butyrylcholinesterase (BChE; IC50 = 0.008–0.041 μM), which may be favorable for AD treatment. Inhibitory activities towards the NMDA receptors and AChE were in the same micromolar range, which may be beneficial for equal dosing against multiple targets in AD patients.

Double "open and Shut" Transformation of γ-Carbolines Triggered by Ammonium Salts: One-Pot Synthesis of Multiheterocyclic Compounds

A novel cascade reaction of indole-2,3-epoxide equivalents with γ-carbolines by utilizing a double "open and shut" transformation to access multiheterocyclic compounds containing both isotryptamines and pyrimido[1,6-a]indoles has been developed. This strategy utilizes the in situ formation of a bulky quaternary ammonium salt via ammonium exchange, which undergoes Hofmann elimination/vinylogous Mannich/retro-Mannich/cyclization cascade sequences.

New route of benzyne cyclization for synthesis of 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole derivatives avoiding highly toxic aryl hydrazines

A new route for the regioselective synthesis of 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole derivatives was developed based on cyclization of 3-chlorophenylimine-N-alkyl-4-piperidones by "the complex bases" of NaNH2 or KNH2. The procedure was performed under variable reaction conditions in inert proton-free solvents, such as THF, dioxane, 1,2-dimethoxyethane, toluene, and xylene, at temperatures varying from 20C to boiling point of the solvent used. Toxic arylhydrazine intermediates occurring in the classical Fischer indole synthesis are avoided.

Second-generation histone deacetylase 6 inhibitors enhance the immunosuppressive effects of Foxp3+ T-regulatory cells

Second-generation Tubastatin A analogues were synthesized and evaluated for their ability to inhibit selectively histone deacetylase 6 (HDAC6). Substitutions to the carboline cap group were well-tolerated with substitution at the 2-position of both β- and γ-carbolines being optimal for HDAC6 activity and selectivity. Some compounds in this series were determined to have subnanomolar activity at HDAC6 with more than 7000 fold selectivity for HDAC6 versus HDAC1. Selected compounds were then evaluated for their ability to augment the immunosuppressive effect of Foxp3+ regulatory T cells. All compounds tested were found to enhance the ability of regulatory T cells to inhibit the mitotic division of effector T cells both in vitro and in vivo, suggesting that further investigation into the use of these compounds for the treatment of autoimmune disorders is warranted.

PROCESS FOR THE PREPARATION OF 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLE DERIVATIVES

The value of the invention is the application of the cyclization of Schiff-bases of the general formula (3a-i), where R1 - R8 are substituents defined in example 1, whereby R9 = Cl using complex bases of amides of group I of the periodic table (NaNH2, KNH2) from 2.1 - 5 equiv. and alcoholates of group I of the periodic table (t-BuONa, tBuOK) from 0.05 - 2 equiv. with the advantage of application of 3 equiv. of NaNH2 and 0.05 equiv. of t-BuONa, or their mixtures with PEG (m.w. = 500 - 6000), or crown ethers, or catalysts of phase transfer lithium in inert proton-free diluents, such as benzene, cyclohexane, toluene, xylene, 1,2-dimethoxyethane, dioxane, etc., with the advantage of using THF, at a temperature from 20 °C to boiling point of the diluent used, or with the application of organo-metallic bases such as LDA, t-BuLi in inert proton-free diluents at a temperature from -80°C to 25 °C.

ARYL CARBOXAMIDE DERIVATIVES AS SODIUM CHANNEL INHIBITORS FOR TREATMENT OF PAIN

The present invention provides compounds that are inhibitors of voltage-gated sodium channels (Nav), in particular Nav 1.7, and are therefore useful for the treatment of diseases treatable by inhibition of these channels, in particular, chronic pain disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Synthesis and biological activity of N-aroyl-tetrahydro-γ-carbolines

Research on dual inhibitors of both 5-LOX and COXs gained interest due to the overexpressions of these enzymes during the malignant state of the evolution of prostate cancer. In order to take part in this research, new N-aroyl-tetrahydro-γ-carbolines issued from the modification of Indomethacin have been synthesised. As for the NSAIDs, the compounds have been tested for their activity against COX1, COX2 plus against 5-LOX and against the proliferation of malignant prostate cancer. Interesting cytotoxic activities and selectivities of some tetrahydro-γ-carboline derivatives have been obtained.

METHODS AND COMBINATION THERAPIES FOR TREATING ALZHEIMER'S DISEASE

The invention provides methods and combination therapies for treating and/or preventing and/or slowing the onset and/or development of Alzheimer's disease using a hydrogenated pyrido (4,3-b) indole (e.g., dimebon) in conjunction with another compound, pharmaceutically acceptable salt thereof or therapy for Alzheimer's disease.

Methods and compositions for treating Huntington's disease

The invention provides method for treating Huntington's disease, slowing the onset and/or development and/or progression of Huntington's disease or preventing the development of Huntington's disease using hydrogenated pyrido[4,3-b]indoles, including dimebon.