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

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

[Display omitted] A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-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 a...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2021-04, Vol.38, p.127872-127872, Article 127872
Hauptverfasser: 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
Format: Artikel
Sprache:eng
Schlagworte:
5-HT2C agonists
CNS drugs
Lorcaserin
Naphthyridine
Tricyclic amines
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Zusammenfassung:[Display omitted] A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-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-5H-pyrazino[1,2-a][1,8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2021.127872