50541-93-0Relevant articles and documents
An improved scalable process for synthesis of piperidin-4-yl-carbamates
Devarasetty, Sitaramaiah,Nunna, Rambabu,Janni, Ravi,Pothuri, Vijai Varma,Suraparaju, Raghu Ram
, p. 775 - 777 (2018)
An efficient route for the synthesis of methyl piperidine-4-yl-carbamate para-toluene sulfonate salt has been developed. The synthesis involves the reductive amination of 1-benzylpiperidin-4-one with ammonia using Raney-Ni as a catalyst followed by de-protection of benzyl group and finally by making its salt. The advantage of this methodology includes use of easily available commercial raw materials and shorter reaction times with high yields makes this process most viable for large scale manufacturing methyl piperidine-4-yl-carbamate salts.
Claulansine F-donepezil hybrids as anti-alzheimer’s disease agents with cholinergic, free-radical scavenging, and neuroprotective activities
Chen, Xinyi,Li, Chuangjun,Liu, Ke,Ma, Jie,Wang, Weiping,Wang, Xiaoliang,Yang, Jingzhi,Zang, Yingda,Zhang, Dongming
, (2021/05/31)
The multifactorial nature of Alzheimer’s disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63-4.62 μM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol- 5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.
Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy
Perone, Rosaria,Albertini, Claudia,Uliassi, Elisa,Di Pietri, Flaminia,de Sena Murteira Pinheiro, Pedro,Petralla, Sabrina,Rizzardi, Nicola,Fato, Romana,Pulkrabkova, Lenka,Soukup, Ondrej,Tramarin, Anna,Bartolini, Manuela,Bolognesi, Maria Laura
, p. 187 - 198 (2020/09/02)
Thanks to the widespread use and safety profile of donepezil (1) in the treatment of Alzheimer's disease (AD), one of the most widely adopted multi-target-directed ligand (MTDL) design strategies is to modify its molecular structure by linking a second fragment carrying an additional AD-relevant biological property. Herein, supported by a proposed combination therapy of 1 and the quinone drug idebenone, we rationally designed novel 1-based MTDLs targeting Aβ and oxidative pathways. By exploiting a bioisosteric replacement of the indanone core of 1 with a 1,4-naphthoquinone, we ended up with a series of highly merged derivatives, in principle devoid of the “physicochemical challenge” typical of large hybrid-based MTDLs. A preliminary investigation of their multi-target profile identified 9, which showed a potent and selective butyrylcholinesterase inhibitory activity, together with antioxidant and antiaggregating properties. In addition, it displayed a promising drug-like profile.