70539-84-3Relevant academic research and scientific papers
Evaluation of γ-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors
Arndt, Hans-Dieter,Gaube, Friedemann,Raztsou, Ihar,Robaa, Dina,Rohrbach, Marius M.,Sager, Henrike,Schwarthoff, Sigrid,Tischer, Nicolas,Winckler, Thomas,Sch?tz, Bianca
, (2021/08/16)
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.
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
Kovacikova, Lucia,Stefek, Milan
, p. 1257 - 1263 (2015/04/27)
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.
Ruthenium-catalyzed γ-carbolinium ion formation from aryl azides; Synthesis of dimebolin
Dong, Huijun,Latka, Regina T.,Driver, Tom G.
, p. 2726 - 2729 (2011/06/28)
A range of γ-carbolines were produced stereoselectively from ruthenium(III)-catalyzed reactions of 3-pyridyl substituted aryl azides. Other catalysts and conditions were neither as selective nor as high-yielding. This method was used to synthesize dimebolin in a concise and efficient manner.
PROCESS FOR THE PREPARATION OF 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLE DERIVATIVES
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Page/Page column 13-14, (2011/11/30)
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.
