Discovery of a Potent, Dual Serotonin and Norepinephrine Reuptake Inhibitor

详细信息    查看全文

• 作者：Nicolas Dreyfus ; Jason K. Myers ; Valentina O. Badescu ; Oscar de Frutos ; Maria Luz de la Puente ; Chunjin Ding ; Sandra A. Filla ; Karsten Fynboe ; Douglas L. Gernert ; Beverly A. Heinz ; Susan K. Hemrick-Luecke ; Kirk W. Johnson ; Michael P. Johnson ; Pilar L贸pez ; Patrick L. Love ; Laura J. Martin ; Thierry Masquelin ; Michael J. McCoy ; Javier Mendiola ; Denise Morrow ; Mark Muhlhauser ; Gustavo Pascual ; Thomas J. Perun ; Lance A. Pfeifer ; Lee A. Phebus ; Simon J. Richards ; Juan Antonio Rinc贸n ; Eric P. Seest ; Jikesh Shah ; Jia Shaojuan ; Rosa Maria A. Simmons ; Gregory A. Stephenson ; Eric G. Tromiczak ; Linda K. Thompson ; Magnus W. Walter ; Wayne W. Weber ; Hamideh Zarrinmayeh ; Craig E. Thomas ; Elizabeth Joshi ; Smriti Iyengar ; Anette M. Johansson
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：June 13, 2013
• 年：2013
• 卷：4
• 期：6
• 页码：560-564
• 全文大小：274K
• 年卷期：v.4,no.6(June 13, 2013)
• ISSN：1948-5875

文摘

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鈥揹rug 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 properties, and retains inhibitory activity in the formalin model of pain behavior. Compound 1 thus represents a potential new probe to explore utility of SNRIs in central nervous system disorders, including chronic pain conditions.

Keywords:

SERT; NET; dual; reuptake inhibitor; SNRI; SERT RO; 伪-MMT; pain