Discovery of (R)-9-Ethyl-1, 3, 4, 10b-tetrahydro-7-trifluoromethylpyrazino [2, 1-a] isoindol-6 (2 H)-one, a Selective, Orally Active Agonist of the 5-HT2C Receptor

…, G Wu, G Zhang, E Zuvich, MA Thomas…

Index: Wacker, Dean A.; Varnes, Jeffrey G.; Malmstrom, Sarah E.; Cao, Xueying; Hung, Chen-Pin; Ung, Thao; Wu, Ginger; Zhang, Ge; Zuvich, Eva; Thomas, Michael A.; Keim, William J.; Cullen, Mary Jane; Rohrbach, Kenneth W.; Qu, Qinling; Narayanan, Rangaraj; Rossi, Karen; Janovitz, Evan; Lehman-McKeeman, Lois; Malley, Mary F.; Devenny, James; Pelleymounter, Mary Ann; Miller, Keith J.; Robl, Jeffrey A. Journal of Medicinal Chemistry, 2007 , vol. 50, # 6 p. 1365 - 1379

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Citation Number: 28

Abstract

Robust pharmaceutical treatment of obesity has been limited by the undesirable side-effect profile of currently marketed therapies. This paper describes the synthesis and optimization of a new class of pyrazinoisoindolone-containing, selective 5-HT2C agonists as antiobesity agents. Key to optimization of the pyrazinoisoindolone core was the identification of the appropriate substitution pattern and functional groups which led to the discovery of (R)-9- ...