73-63-2Relevant articles and documents
Metal-free synthesis of β-aminoketones by the reductive hydroamination of ynones
Fu, Rui,Liu, Yu,Wu, Tao,Zhang, Xinyu,Zhu, Yang,Luo, Jiangbin,Zhang, Zhengyu,Jiang, Yaojia
, p. 3525 - 3528 (2022/03/31)
This study describes a cascade method for the synthesis of β-aminoketones through the reductive hydroamination of alkynes under very mild metal-free conditions. It allows for the rapid conversion of ynones and amines into corresponding β-aminoketones with a broad substrate scope and diverse functionalities. This straightforward and easy-to-handle reaction process can be successfully applied for the synthesis of Proroxan and Propipocaine, offering a potential option for the synthesis of drug molecules with the β-aminoketone skeleton.
Mechanistic studies on counter-ionic effects of camphorsulfonate-based ionic liquids on kinetics, thermodynamics and stereoselectivity of β-amino carbonyl compounds
Hamzah, Ahmad Sazali,Jabeen, Erum,Leveque, Jean-Marc,Sardar, Sabahat,Wilfred, Cecilia Devi
, (2020/10/08)
Catalysis is important in various applications of organic chemistry and its output product control for stereoselective compounds is outrageous. Establishment of experimental facts of stereoselective compounds from catalysis and their validation using theoretical evidences is the key to understand various mechanisms of optically active compounds. A family of new ionic liquids (ILs) with various imidazolium cations and camphorsulfonate anion as environmentally benign liquid salts have been synthesized and deployed for catalysis of β-amino carbonyl compounds. The products were formed using ILs as a homogeneous catalyst with excellent product yield and diastereoselectivity. The effect of counter ions, Hammett acidity and viscosity of ILs along with solvent and temperature are explored in terms of reaction kinetics and product yields. Density functional theory (DFT) was used to investigate thermodynamical study of mechanistic pathway of the reaction. The DFT calculations predicted that the catalysis mechanism involved both counterions of the IL. Moreover, it is evidenced that the syn-pathway required lower activation energy while anti-pathway led to thermodynamically stable product. This study explores new avenues for using ILs as potential homogeneous catalysts for the production of stereoselective species.
Identification of dual Sigma1 receptor modulators/acetylcholinesterase inhibitors with antioxidant and neurotrophic properties, as neuroprotective agents
Rui, Marta,Rossino, Giacomo,Coniglio, Stefania,Monteleone, Stefania,Scuteri, Arianna,Malacrida, Alessio,Rossi, Daniela,Catenacci, Laura,Sorrenti, Milena,Paolillo, Mayra,Curti, Daniela,Venturini, Letizia,Schepmann, Dirk,Wünsch, Bernhard,Liedl, Klaus R.,Cavaletti, Guido,Pace, Vittorio,Urban, Ernst,Collina, Simona
, p. 353 - 370 (2018/09/21)
In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed with antioxidant and neurotrophic properties, potentially able to counteract neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate the pharmacophoric elements of RRC-33, a S1R modulator developed by us, donepezil, a well-known AChE inhibitor, and curcumin, a natural antioxidant compound with neuroprotective properties. A small library of compounds was synthesized and preliminary in vitro screening performed. Some compounds showed good S1R binding affinity, selectivity towards S2R and N-Methyl-D-Aspartate (NMDA) receptor, AChE relevant inhibiting activity and are potentially able to bypass the BBB, as predicted by the in silico study. For the hits 10 and 20, the antioxidant profile was assessed in SH-SY5Y human neuroblastoma cell lines by evaluating their protective effect against H2O2 cytotoxicity and reactive oxygen species (ROS) production. Tested compounds resulted effective in decreasing ROS production, thus ameliorating the cellular survival. Moreover, compounds 10 and 20 showed to be effective in promoting the neurite elongation of Dorsal Root Ganglia (DRG), thus demonstrating a promising neurotrophic activity. Of note, the tested compounds did not show any cytotoxic effect at the concentration assayed. Relying on these encouraging results, both compounds will undergo a structure optimization program for the development of therapeutic candidates for neurodegenerative diseases treatment.
