An octahydro-cyclopenta[c]pyrrole series of inhibitors of the type 1 glycine transporter
| Autor: | Christopher J. Schmidt, Sanner Mark Allen, Karen M. Ward, Susan E. Drozda, James J. Valentine, John A. Lowe, Shari L. DeNinno, Don Tunucci, F. David Tingley |
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| Rok vydání: | 2009 |
| Předmět: |
Isostere
Stereochemistry Clinical Biochemistry Substituent Pharmaceutical Science Cyclopentanes Biochemistry Chemical synthesis Cell Line Glycine transporter chemistry.chemical_compound Dogs In vivo Glycine Plasma Membrane Transport Proteins Microsomes Drug Discovery Animals Humans Pyrroles Molecular Biology Pyrrole Organic Chemistry Transporter chemistry Glycine Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(3) |
| ISSN: | 1464-3405 |
| Popis: | We describe a novel series of inhibitors of the type 1 glycine transporter (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro-cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c-pentyl), 4-F substituent may serve as a surrogate for the widely used 3-trifluoromethoxy group, suggesting its application as an isostere for future medicinal chemistry studies. |
| Databáze: | OpenAIRE |
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