| Literature DB >> 24900709 |
Nicolas Dreyfus1, Jason K Myers2, Valentina O Badescu2, Oscar de Frutos3, Maria Luz de la Puente3, Chunjin Ding2, Sandra A Filla2, Karsten Fynboe4, Douglas L Gernert2, Beverly A Heinz2, Susan K Hemrick-Luecke2, Kirk W Johnson2, Michael P Johnson2, Pilar López3, Patrick L Love4, Laura J Martin2, Thierry Masquelin2, Michael J McCoy2, Javier Mendiola3, Denise Morrow2, Mark Muhlhauser2, Gustavo Pascual3, Thomas J Perun2, Lance A Pfeifer2, Lee A Phebus2, Simon J Richards1, Juan Antonio Rincón3, Eric P Seest2, Jikesh Shah2, Jia Shaojuan2, Rosa Maria A Simmons2, Gregory A Stephenson2, Eric G Tromiczak2, Linda K Thompson2, Magnus W Walter1, Wayne W Weber2, Hamideh Zarrinmayeh2, Craig E Thomas2, Elizabeth Joshi2, Smriti Iyengar2, Anette M Johansson2.
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.Entities:
Keywords: NET; SERT; SERT RO; SNRI; dual; pain; reuptake inhibitor; α-MMT
Year: 2013 PMID： 24900709 PMCID： PMC4027471 DOI： 10.1021/ml400049p
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345