Synthesis and SAR of sulfoxide substituted carboxyquinolines as NK3 receptor antagonists

✍ Scribed by Hui Xiong; James Kang; James M. Woods; John P. McCauley Jr.; Gerard M. Koether; Jeffrey S. Albert; Lindsay Hinkley; Yan Li; Reto A. Gadient; Thomas R. Simpson

• Book ID: 104005086
• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 553 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.11.003

✦ Synopsis

The neurokinin-3 (NK3) receptor is regarded as a potential novel target for treating patients with schizophrenia. Herein we report the synthesis and SAR of a series of C3-alkylsulfoxide substituted quinolines as potent NK3 receptor antagonists. These compounds have excellent NK3 functional activity, good selectivity and drug-like properties. Several key compounds have good in vitro/in vivo DMPK characteristics, and are active in a gerbil locomotor activity model.