Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors

  • Bioorg Med Chem Lett. 2008 Dec 1;18(23):6062-6. doi: 10.1016/j.bmcl.2008.10.025.
Linda M Bannwart  1 ,  David S Carter ,  Hai-Ying Cai ,  Jason C Choy ,  Robert Greenhouse ,  Saul Jaime-Figueroa ,  Pravin S Iyer ,  Clara J Lin ,  Eun Kyung Lee ,  Matthew C Lucas ,  Stephen M Lynch ,  Ann Marie Madera ,  Amy Moore ,  Kerem Ozboya ,  Lubica Raptova ,  Ralf Roetz ,  Ryan C Schoenfeld ,  Karin Ann Stein ,  Sandra Steiner ,  Marzia Villa ,  Robert J Weikert ,  Yansheng Zhai
Affiliations
  • 1. Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
PMID: 18954985 DOI: 10.1016/j.bmcl.2008.10.025
Abstract

A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.