216854-24-9Relevant articles and documents
Rhodium-Catalyzed Asymmetric Hydrogenation of N-(1-benzylpiperidin-3-yl)-enamides: An Efficient Access to Valuable Enantioenriched 3-Aminopiperidine Derivatives
Royal, Titouan,Dudognon, Yohan,Berhal, Farouk,Bastard, Yvon,Boudet, Bernard,Ayad, Tahar,Ratovelomanana-Vidal, Virginie
, p. 2009 - 2013 (2016)
An efficient synthetic entry to enantioenriched 3-aminopiperidine derivatives using rhodium-catalyzed asymmetric hydrogenation of N-(1-benzylpiperidin-3-yl)enamides is described. This method provides an atom-economical and attractive route to both enantiomers of the valuable 3-aminopiperidine moiety, which is an important structural unit that can be found in many natural products and pharmaceutical drugs encompassing a broad range of biological activities. Under optimized reaction conditions, the targeted 3-aminopiperidine derivatives were obtained in high yields up to 92% and with enantiomeric excesses up to 96% after a single crystallization.
Synthetic process of anti-hyperglycemic drug intermediate R-3-amino-piperidine dihydrochloride
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, (2019/11/12)
The invention relates to a synthetic process of an anti-hyperglycemic drug intermediate R-3-amino-piperidine dihydrochloride. The synthetic process comprises the steps: using inexpensive L-glutamic acid as a starting material, and performing esterification, amino protection, reduction, hydroxyl protection, substitution, cyclization and removal of protecting groups for amino groups so as to obtainthe R-3-amino-piperidine dihydrochloride. Compared with the prior art, the synthetic process has cheap and easily available raw materials, good selectivity, good atomic economy, high total yield and mild reaction conditions, and is suitable for industrial production.
Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation
Panek, Dawid,Wi?ckowska, Anna,Wichur, Tomasz,Bajda, Marek,Godyń, Justyna,Jończyk, Jakub,Mika, Kamil,Janockova, Jana,Soukup, Ondrej,Knez, Damijan,Korabecny, Jan,Gobec, Stanislav,Malawska, Barbara
, p. 676 - 695 (2016/10/13)
The complexity of Alzheimer's disease (AD) calls for search of multifunctional compounds as potential candidates for effective therapy. A series of phthalimide and saccharin derivatives linked by different alicyclic fragments (piperazine, hexahydropyrimidine, 3-aminopyrrolidine or 3-aminopiperidine) with phenylalkyl moieties attached have been designed, synthesized, and evaluated as multifunctional anti-AD agents with cholinesterase, β-secretase and β-amyloid inhibitory activities. In?vitro studies showed that the majority of saccharin derivatives with piperazine moiety and one phthalimide derivative with 3-aminopiperidine fragment exhibited inhibitory potency toward acetylcholinesterase (AChE) with EeAChE IC50values ranging from 0.83?μM to 19.18?μM. The target compounds displayed inhibition of human β-secretase-1 (hBACE1) ranging from 26.71% to 61.42% at 50?μM concentration. Among these compounds, two multifunctional agents (26, [2-(2-(4-benzylpiperazin-1-yl)ethyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide] and 52, 2-(2-(3-(3,5-difluorobenzylamino)piperidin-1-yl)ethyl)isoindoline-1,3-dione) have been identified. Compound 26 exhibited the highest inhibitory potency against EeAChE (IC50?=?0.83?μM) and inhibitory activity against hBACE1 (33.61% at 50?μM). Compound 52 is a selective AChE inhibitor (IC50 AChE?=?6.47?μM) with BACE1 inhibitory activity (26.3% at 50?μM) and it displays the most significant Aβ anti-aggregating properties among all the obtained compounds (39% at 10?μM). Kinetic and molecular modeling studies indicate that 26 may act as non-competitive AChE inhibitor able to interact with both catalytic and peripheral active site of the enzyme.
