Evaluation of 纬-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors was written by Schwarthoff, Sigrid;Tischer, Nicolas;Sager, Henrike;Schaetz, Bianca;Rohrbach, Marius M.;Raztsou, Ihar;Robaa, Dina;Gaube, Friedemann;Arndt, Hans-Dieter;Winckler, Thomas. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Recommanded Product: 5094-12-2 This article mentions the following:
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-纬-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 纬-carbolines linked to phenothiazine via a propionyl spacer. These compounds were superior to the previously characterized bis-纬-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渭M. In addition, these new compounds displayed considerable selectivity for the inhibition of butyrylcholinesterase (BChE; IC50 = 0.008-0.041渭M), 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. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Recommanded Product: 5094-12-2).
2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.Recommanded Product: 5094-12-2
Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles