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

Add time:07/11/2019    Source:sciencedirect.com

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.

We also recommend Trading Suppliers and Manufacturers of 2-METHYL-1-(2-MORPHOLIN-4-YL-2-OXO-ETHYL)-1H-INDOLE-3-CARBALDEHYDE (cas 433707-36-9). Pls Click Website Link as below: cas 433707-36-9 suppliers

Prev:Synthesis and self-assembly of Poly(N-octyl benzamide)-μ-poly(ε-caprolactone) miktoarm star copolymers displaying uniform nanofibril morphology
Next:Synthesis and antimicrobial activity of 2-substituted [4-(1,3,4-oxadiazol-2-yl methyl)] phthalazin-1(2H)-one derivatives)