Novel (R)-6, 6a, 7, 8, 9, 10-hexahydro-5H-pyrazino[1, 2-a][1, n]naphthyridines as potent and selective agonists of the 5-HT2C receptor. (15th April 2021)

• Record Type: Journal Article
• Authors: Schrader, Thomas O.; Zhu, Xiuwen; Kasem, Michelle; Ren, Albert; Liu, Chunyan; Wu, Chunrui; Dang, Huong; Le, Minh; Gatlin, Joel; Chase, Kelli; Frazer, John; Whelan, Kevin T.; Grottick, Andrew J.; Hutton, Clayton; Barden, Jeremy; Chen, Chuan; Ortiz, Alvaro; Feichtinger, Konrad; Semple, Graeme
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 38(2021)
• Publication Date: 2021-04-15
• Subjects: 5-HT2C agonists -- Lorcaserin -- Naphthyridine -- CNS drugs -- Tricyclic amines; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.127872
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of novel ( R )-6, 6a, 7, 8, 9, 10-hexahydro-5 H -pyrazino[1, 2- a ][1, n]naphthyridines were identified as potent and selective agonists of the 5-HT2C receptor. Optimizations performed on a previously reported series of racemic tetrahydroquinoline-based tricyclic amines, delivered an advanced drug lead, ( R )-4-(3, 3, 3-trifluoropropyl)-6, 6a, 7, 8, 9, 10-hexahydro-5 H -pyrazino[1, 2- a ][1, 8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.