Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373815 | Bioorganic & Medicinal Chemistry Letters | 2010 | 8 Pages |
Abstract
Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug–drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Matthew C. Lucas, Robert J. Weikert, David S. Carter, Hai-Ying Cai, Robert Greenhouse, Pravin S. Iyer, Clara J. Lin, Eun Kyung Lee, Ann Marie Madera, Amy Moore, Kerem Ozboya, Ryan C. Schoenfeld, Sandra Steiner, Yansheng Zhai, Stephen M. Lynch,