914462-75-2

Upstream product

• 952138-35-1 N,N'-(1',4'-succinyl)-bis-(-)-nor-MEP 
• 1018990-35-6 (-)-N-carboethoxy-nor-meptazinol 
• 952138-56-6 C₂₁H₂₅NO₃ 
• 94666-16-7 (-)-meptazinol 
• 952208-06-9 (S)-3-(3-ethylazepan-3-yl)phenol 

Relevant academic research and scientific papers

Meptazinol Biligand Derivatives and/or their Salts, Preparation Method and Uses Thereof

The present invention belongs to pharmaceutical field. It relates to a novel family of bivalent (?)-meptazinol compounds and/or their salts, as well as the preparation and utilization of the compounds in the treatment of neurodegenerative disorders and dementias such as Alzheimer's Disease (AD). In the present invention, bivalent (?)-meptazinol compounds were synthesized, from the starting material (?)-meptazinol, successively by N-demethylation forming (?)-nor-meptazinol and then by acylation with α,ω-alkanediacyl dihalides or alkylation with α,ω-dihaloalkanes. Results from in vitro cholinesterase inhibiting test and AChE-induced Aβ aggregation test demonstrated that the bivalent (?)-meptazinol compounds and/or their salts were novel bivalent inhibitors of both ACHE and Aβ aggregation. The most potent compound inhibited both ACHE and BCHE at nM level, which was 10000 and 1500 times more potent than (?)-MEP hydrochloride, respectively. It inhibited ACHE-induced Aβ aggregation by a factor of 2 compared with propidium.

MEPTAZINOL BILIGAND DERIVATIVES AND/OR THEIR SALTS, PREPARATION METHOD AND USES THEREOF

The present invention belongs to pharmaceutical field. It relates to a novel family of bivalent (-)-meptazinol compounds and/or their salts, as well as the preparation and utilization of the compounds in the treatment of neurodegenerative disorders and de

Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-β aggregation

Bis-(-)-nor-meptazinols (bis-(-)-nor-MEPs) 5 were designed and synthesized by connecting two (-)-nor-MEP monomers with alkylene linkers of different lengths via the secondary amino groups. Their acetylcholinesterase (AChE) inhibitory activities were more greatly influenced by the length of the alkylene chain than butyrylcholinesterase (BChE) inhibition. The most potent nonamethylene-tethered dimer 5h exhibited low-nanomolar IC50 values for both ChEs, having a 10 000-fold and 1500-fold increase in inhibition of AChE and BChE compared with (-)-MEP. Molecular docking elucidated that 5h simultaneously bound to the catalytic and peripheral sites in AChE via hydrophobic interactions with Trp86 and Trp286. In comparison, it folded in the large aliphatic cavity of BChE because of the absence of peripheral site and the enlargement of the active site. Furthermore, 5h and 5i markedly prevented the AChE-induced Aβ aggregation with IC50 values of 16.6 and 5.8 μM, similar to that of propidium (IC50 = 12.8 μM), which suggests promising disease-modifying agents for the treatment of AD patients.