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.

使用2-硝基丙-1-烯基苯的不对称迈克尔加成反应合成了由2-（5-甲基-4-苯基-2-氧吡咯烷-1-基）-乙酰胺对映体代表的sigma-1受体的新型正构构调节剂丙二酸。继甲基的色谱分离赤-和苏式-4-硝基-3 - [R -和3 š -phenylpentanoate非对映体，通过其还原性环化得到为5-甲基-4-苯基吡咯烷-2-酮的对映体和连接目标化合物乙酰胺基团与杂环氮原子相连。由sigma-1受体激动剂PRE-084引起的电刺激大鼠输精管收缩的实验表明（4 R，5 S）和（4 R，5 R）-2-（5-甲基-4-苯基-2-氧吡咯烷-1-基）-乙酰胺在2-吡咯烷酮环的C-4手性中心具有R-构型比其光学对映体更有效的sigma-1受体正变构调节剂。