Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370464 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
Abstract
Structure–activity studies have led to a discovery of 3-(4-pyridyl)methyl ether derivative 9d that has 25- to 50-fold greater functional potency than R-baclofen at human and rodent GABAB receptors in vitro. Mouse hypothermia studies confirm that this compound crosses the blood–brain barrier and is approximately 50-fold more potent after systemic administration.
Graphical abstractNovel substituted analogs or R-baclofen was explored and a highly potent agonist was discovered. (9d pEC50 = 8.5). Characterization of 9d showed it to be 25- to 50-fold more potent than R-baclofen in vitro and in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Feng Xu, Ge Peng, Thu Phan, Usha Dilip, Jian Lu Chen, Tania Chernov-Rogan, Xuexiang Zhang, Kent Grindstaff, Thamil Annamalai, Kerry Koller, Mark A. Gallop, David J. Wustrow,