2. Academic Validation
  3. Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor

Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor

  • ACS Med Chem Lett. 2013 May 7;4(6):560-4. doi: 10.1021/ml400049p.
Nicolas Dreyfus 1,  Jason K Myers 2,  Valentina O Badescu 2,  Oscar de Frutos 3,  Maria Luz de la Puente 3,  Chunjin Ding 2,  Sandra A Filla 2,  Karsten Fynboe 4,  Douglas L Gernert 2,  Beverly A Heinz 2,  Susan K Hemrick-Luecke 2,  Kirk W Johnson 2,  Michael P Johnson 2,  Pilar López 3,  Patrick L Love 4,  Laura J Martin 2,  Thierry Masquelin 2,  Michael J McCoy 2,  Javier Mendiola 3,  Denise Morrow 2,  Mark Muhlhauser 2,  Gustavo Pascual 3,  Thomas J Perun 2,  Lance A Pfeifer 2,  Lee A Phebus 2,  Simon J Richards 1,  Juan Antonio Rincón 3,  Eric P Seest 2,  Jikesh Shah 2,  Jia Shaojuan 2,  Rosa Maria A Simmons 2,  Gregory A Stephenson 2,  Eric G Tromiczak 2,  Linda K Thompson 2,  Magnus W Walter 1,  Wayne W Weber 2,  Hamideh Zarrinmayeh 2,  Craig E Thomas 2,  Elizabeth Joshi 2,  Smriti Iyengar 2,  Anette M Johansson 2
Affiliations

Affiliations

  • 1 Research and Development, Eli Lilly and Company Ltd. , Sunninghill Road, Windlesham, Surrey GU20 6PH, United Kingdom.
  • 2 Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
  • 3 Lilly S.A. , Centro de Investigación, Avda. de la Industria, 30, Alcobendas-Madrid 28108, Spain.
  • 4 Covance, Inc. , Greenfield, Indiana 46140, United States.
PMID: 24900709 DOI: 10.1021/ml400049p
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 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

NET; SERT; SERT RO; SNRI; dual; pain; reuptake inhibitor; α-MMT.

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