2683-56-9Relevant academic research and scientific papers
Design, synthesis and evaluation of phthalide alkyl tertiary amine derivatives as promising acetylcholinesterase inhibitors with high potency and selectivity against Alzheimer's disease
Cao, Zhongcheng,Deng, Yong,Li, Yan,Luo, Li,Qiang, Xiaoming,Song, Qing,Tan, Zhenghuai
, (2020/03/13)
A series of phthalide alkyl tertiary amine derivatives were designed, synthesized and evaluated as potential multi-target agents against Alzheimer's disease (AD). The results indicated that almost all the compounds displayed significant AChE inhibitory and selective activities. Besides, most of the derivatives exhibited increased self-induced Aβ1-42 aggregation inhibitory activity compared to the lead compound DL-NBP, and some compounds also exerted good antioxidant activity. Specifically, compound I-8 showed the highest inhibitory potency toward AChE (IC50 = 2.66 nM), which was significantly better than Donepezil (IC50 = 26.4 nM). Moreover, molecular docking studies revealed that compound I-8 could bind to both the catalytic active site and peripheral anionic site of AChE. Furthermore, compound I-8 displayed excellent BBB permeability in vitro. Importantly, the step-down passive avoidance test indicated that I-8 significantly reversed scopolamine-induced memory deficit in mice. Collectively, these results suggested that I-8 might be a potent and selective AChE inhibitor for further anti-AD drug development.
Platinum-Catalyzed, Terminal-Selective C(sp3)-H Oxidation of Aliphatic Amines
Lee, Melissa,Sanford, Melanie S.
supporting information, p. 12796 - 12799 (2015/10/28)
This Communication describes the terminal-selective, Pt-catalyzed C(sp3)-H oxidation of aliphatic amines without the requirement for directing groups. CuCl2 is employed as a stoichiometric oxidant, and the reactions proceed in high yield at Pt loadings as low as 1 mol%. These transformations are conducted in the presence of sulfuric acid, which reacts with the amine substrates in situ to form ammonium salts. We propose that protonation of the amine serves at least three important roles: (i) it renders the substrates soluble in the aqueous reaction medium; (ii) it limits binding of the amine nitrogen to Pt or Cu; and (iii) it electronically deactivates the C-H bonds proximal to the nitrogen center. We demonstrate that this strategy is effective for the terminal-selective C(sp3)-H oxidation of a variety of primary, secondary, and tertiary amines.
Reductive hydroxyalkylation/alkylation of amines with lactones/esters
Wang, Yu-Huang,Ye, Jian-Liang,Wang, Ai-E,Huang, Pei-Qiang
experimental part, p. 6504 - 6511 (2012/09/08)
We have developed a one-pot method for the direct intermolecular reductive hydroxyalkylation or alkylation of amines using lactones or esters as the hydroxyalkylating/alkylating reagents. The method is based on the in situ amidation of lactones/esters with DIBAL-H-amine complex (for primary amines) or DIBAL-H-amine hydrochloride salt complex (for secondary amines), followed by reduction of the amides with an excess of DIBAL-H. Different from the reduction of Weinreb amides with DIBAL-H where aldehydes are formed, the reduction of the in situ formed Weinreb amides yielded amines. Moreover, this method is not limited to Weinreb amides, instead, it also works for other amides in general. A plausible mechanism is suggested to account for the outcome of the reactions.
Novel antagonists of serotonin-4 receptors: Synthesis and biological evaluation of pyrrolothienopyrazines
Lemaitre, Stephane,Lepailleur, Alban,Bureau, Ronan,Butt-Gueulle, Sabrina,Lelong-Boulouard, Veronique,Duchatelle, Pascal,Boulouard, Michel,Dumuis, Aline,Daveu, Cyril,Lezoualc'h, Frank,Pfeiffer, Bruno,Dauphin, Francois,Rault, Sylvain
scheme or table, p. 2607 - 2622 (2009/09/06)
Based on the definition of a 5-HT4 receptor antagonist pharmacophore, a series of pyrrolo[1,2-a]thieno[3,2-e] and pyrrolo[1,2-a]thieno[2,3-e] pyrazine derivatives were designed, prepared, and evaluated to determine the properties necessary for high-affinity binding to 5-HT4 receptors. The compounds were synthesized by substituting the chlorine atom of the pyrazine ring with various N-alkyl-4-piperidinylmethanolates. They were evaluated in binding assays with [3H]GR113808 (1) as the 5-HT4 receptor radioligand. The affinity values (Ki or inhibition percentages) were affected by both the substituent on the aromatic ring and the substituent on the lateral piperidine chain. A methyl group on the tricyclic ring produced a marked increase in affinity while an N-propyl or N-butyl group gave compounds with nanomolar affinities. Among the most potent ligands, 34d was selected for further pharmacological studies and evaluated in vivo. This compound acts as an antagonist/weak partial agonist in COS-7 cells stably expressing the 5-HT4(a) receptor and is of great interest as a peripheral antinociceptive agent.
Action d'organometalliques fonctionnels sur les gem-aminoethers et les sels d'immonium. II. Synthese d'amines γ-fonctionnelles α-acetyleniques, α-ethyleniques Z ou E et saturees
Courtois, Gilles,Miginiac, Philippe
, p. 21 - 27 (2007/10/02)
α-Functional acetylenic organomagnesium compounds easily react with gem-aminoethers and immonium salts to lead to α-acetylenic γ-functional amines in good yields.By partial reduction, these amines selectively produce Z or E α-unsaturated γ-functional amines and by complete reduction, they lead to saturated γ-functional amines.
CLEAVAGE OF N-METHOXYMETHYLAMMONIUM SALTS. III. TRANSFORMATION OF AMMONIUM SALT DERIVATIVES OF ALIPHATIC AMINO ALCOHOLS IN DIMETHYL SULFOXIDE
Bystrova, L. P.,Kuznetsov, S. G.,Chigareva, S. M.
, p. 1549 - 1553 (2007/10/02)
The dealkylation of methoxymethyl quaternary ammonium salts of some aliphatic amino alcohols in DMSO leads to the simultaneous formation of the hydrohalides of methyl(aminoalkyl)formals and the corresponding amino alcohols.The formals are formed by an intermolecular mechanism.
