Discovery of a Potent, Dual Serotonin and Norepinephrine Reuptake Inhibitor

…, SK Hemrick-Luecke, KW Johnson…

Index: Dreyfus, Nicolas; Myers, Jason K.; Badescu, Valentina O.; De Frutos, Oscar; De La Puente, Maria Luz; Ding, Chunjin; Filla, Sandra A.; Fynboe, Karsten; Gernert, Douglas L.; Heinz, Beverly A.; Hemrick-Luecke, Susan K.; Johnson, Kirk W.; Johnson, Michael P.; Lopez, Pilar; Love, Patrick L.; Martin, Laura J.; Masquelin, Thierry; McCoy, Michael J.; Mendiola, Javier; Morrow, Denise; Muhlhauser, Mark; Pascual, Gustavo; Perun, Thomas J.; Pfeifer, Lance A.; Phebus, Lee A.; Richards, Simon J.; Rincon, Juan Antonio; Seest, Eric P.; Shah, Jikesh; Shaojuan, Jia; Simmons, Rosa Maria A.; Stephenson, Gregory A.; Tromiczak, Eric G.; Thompson, Linda K.; Walter, Magnus W.; Weber, Wayne W.; Zarrinmayeh, Hamideh; Thomas, Craig E.; Joshi, Elizabeth; Iyengar, Smriti; Johansson, Anette M. ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 6 p. 560 - 564

Full Text: HTML

Citation Number: 4

Abstract

The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug–drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME ...