Discovery of novel, selective, functionalized 5-(2-(5-arylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethyl)-γ-butyrolactone sigma-2 ligands

被引：1
作者：
Blass, Benjamin E. [1 ]
Blattner, Kevin M. [2 ]
Gordon, John C. [1 ]
Elokely, Khaled M. [3 ]
Pippin, Douglas A. [2 ]
Canney, Daniel J. [1 ]
机构：
[1] Temple Sch Pharm, Dept Pharmaceut Sci, Moulder Ctr Drug Discovery Res, Philadelphia, PA 19140 USA
[2] Praeventix Inc, 665 Stockton Dr,Suite 200H, Exton, PA 19341 USA
[3] Temple Univ, Dept Chem, Coll Sci & Technol, Inst Computat Mol Sci, Philadelphia, PA 19140 USA
来源：
MEDICINAL CHEMISTRY RESEARCH | 2022年 / 31卷 / 07期
关键词：
Sigma-2; Sigma-1; Sigma receptor; gamma-butyrolactone; ACCURATE DOCKING; PROTEIN; RECEPTOR; GLIDE; IDENTIFICATION;
D O I：
10.1007/s00044-022-02909-8
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The sigma-2 (sigma(2)) receptor was recently identified as the Transmembrane Protein 97 (TMEM97, also known as MAC30 (Meningioma-associated protein)). This protein has been linked to diseases and conditions such as Niemann-Pick disease, schizophrenia, neuropathic pain, traumatic brain injury, cancer, drug addiction, and Alzheimer's disease. The therapeutic utility of sigma(2) ligands is under investigation in numerous laboratories and on-going clinical trials. Herein, we report the identification of a series of novel 5-(2-(5-arylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethyl)-gamma-butyrolactone and their evaluation using in vitro sigma(2) and sigma-1 (sigma(1)) assays to determine their sigma(1)/sigma(2) selectivity profiles, as well as a series of in vitro ADME assays. [GRAPHICS] .
引用
收藏
页码：1209 / 1223
页数：15
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