18085-37-5Relevant articles and documents
Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
van Greunen, Divan G.,Cordier, Werner,Nell, Margo,van der Westhuyzen, Chris,Steenkamp, Vanessa,Panayides, Jenny-Lee,Riley, Darren L.
, p. 671 - 690 (2017/02/10)
A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.
NHC-Catalyzed intramolecular redox amidation for the synthesis of functionalized lactams
Thai, Karen,Wang, Li,Dudding, Travis,Bilodeau, Francois,Gravel, Michel
supporting information; experimental part, p. 5708 - 5711 (2011/03/19)
A very efficient NHC-catalyzed lactamization reaction is reported. For most cases, the ring expansion reaction proceeds to cleanly furnish five- and six-membered N-Ts and N-Bn lactams, without the need for further purification. Evidence is presented suggesting a dual role for the stoichiometric base: (1) deprotonation of the triazolium precatalyst and (2) activation of the nitrogen leaving group through hydrogen bonding.
Enzymatic resolution of methyl N-alkyl-azetidine-2-carboxylates by Candida antarctica lipase-mediated ammoniolysis
Starmans, Wim A. J.,Doppen, Roy G.,Thijs, Lambertus,Zwanenburg, Binne
, p. 429 - 435 (2007/10/03)
A facile method for the synthesis of optically active azetidine-2- carboxylic acid derivatives is presented Racemic N-alkylated azetidine esters are resolved by lipase from Candida antarctica in an ammoniolysis reaction, and both the S-amide and the R-ester are obtained with excellent stereoselectivity.
