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Publikācija: Synthesis and Biological Evaluation of 2-(5-Methyl-4-Phenyl-2-Oxopyrrolidin-1-Yl)-Acetamide Stereoisomers as Novel Positive Allosteric Modulators of Sigma-1 Receptor

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity Unknown
Defending: ,
Publication language English (en)
Title in original language Synthesis and Biological Evaluation of 2-(5-Methyl-4-Phenyl-2-Oxopyrrolidin-1-Yl)-Acetamide Stereoisomers as Novel Positive Allosteric Modulators of Sigma-1 Receptor
Field of research 1. Natural sciences
Sub-field of research 1.4 Chemical sciences
Authors G Veinberg
M Vorona
L Zvejniece
R Vilkersts
E Vavers
Edvards Liepiņš
H Kazoka
Sergejs Beļakovs
Anatolijs Mišņovs
J Kuznecovs
S Vikainis
N Orlova
A Lebedev
Y Ponomaryov
M Dambrova
Keywords 2-(5-Methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide; Enantiomers; Sigma-1 receptor; Agonist; Modulation
Abstract Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4- phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)- acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes.
DOI: 10.1016/j.bmc.2013.03.016
Hyperlink: http://www.sciencedirect.com/science/article/pii/S0968089613002290 
Reference Veinberg, G., Vorona, M., Zvejniece, L., Vilkersts, R., Vavers, E., Liepiņš, E., Kazoka, H., Beļakovs, S., Mišņovs, A., Kuznecovs, J., Vikainis, S., Orlova, N., Lebedev, A., Ponomaryov, Y., Dambrova, M. Synthesis and Biological Evaluation of 2-(5-Methyl-4-Phenyl-2-Oxopyrrolidin-1-Yl)-Acetamide Stereoisomers as Novel Positive Allosteric Modulators of Sigma-1 Receptor. Bioorganic and Medicinal Chemistry, 2013, Vol.21, Iss.10, pp.2764-2771. ISSN 0968-0896. Available from: doi:10.1016/j.bmc.2013.03.016
Additional information Citation count:
ID 17317