17623-96-0Relevant articles and documents
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Friedrich
, p. 1851 (1969)
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N-alkylpiperidine carbamates as potential anti-Alzheimer's agents
Brazzolotto, Xavier,Gobec, Stanislav,Knez, Damijan,Kos, Janko,Nachon, Florian,?akelj, Simon,Juki?, Marko,Ko?ak, Urban,Pi?lar, Anja,Stra?ek, Nika,Zahirovi?, Abida
supporting information, (2020/05/06)
Compounds capable of interacting with single or multiple targets involved in Alzheimer's disease (AD) pathogenesis are potential anti-Alzheimer's agents. In our aim to develop new anti-Alzheimer's agents, a series of 36 new N-alkylpiperidine carbamates was designed, synthesized and evaluated for the inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and monoamine oxidases [monoamine oxidase A (MAO-A and monoamine oxidase B (MAO-B)]. Four compounds are very promising: multiple AChE (IC50 = 7.31 μM), BChE (IC50 = 0.56 μM) and MAO-B (IC50 = 26.1 μM) inhibitor 10, dual AChE (IC50 = 2.25 μM) and BChE (IC50 = 0.81 μM) inhibitor 22, selective BChE (IC50 = 0.06 μM) inhibitor 13, and selective MAO-B (IC50 = 0.18 μM) inhibitor 16. Results of enzyme kinetics experiments showed that despite the carbamate group in the structure, compounds 10, 13, and 22 are reversible and non-time-dependent inhibitors of AChE and/or BChE. The resolved crystal structure of the complex of BChE with compound 13 confirmed the non-covalent mechanism of inhibition. Additionally, N-propargylpiperidine 16 is an irreversible and time-dependent inhibitor of MAO-B, while N-benzylpiperidine 10 is reversible. Additionally, compounds 10, 13, 16, and 22 should be able to cross the blood-brain barrier and are not cytotoxic to human neuronal-like SH-SY5Y and liver HepG2 cells. Finally, compounds 10 and 16 also prevent amyloid β1–42 (Aβ1–42)-induced neuronal cell death. The neuroprotective effects of compound 16 could be the result of its Aβ1–42 anti-aggregation effects.
Dehalogenative Deuteration of Unactivated Alkyl Halides Using D2O as the Deuterium Source
Xia, Aiyou,Xie, Xin,Hu, Xiaoping,Xu, Wei,Liu, Yuanhong
, p. 13841 - 13857 (2019/10/17)
The general dehalogenation of alkyl halides with zinc using D2O or H2O as a deuterium or hydrogen donor has been developed. The method provides an efficient and economic protocol for deuterium-labeled derivatives with a wide substrate scope under mild reaction conditions. Mechanistic studies indicated that a radical process is involved for the formation of organozinc intermediates. The facile hydrolysis of the organozinc intermediates provides the driving force for this transformation.