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Proline bis-amides as potent dual orexin receptor antagonists
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Feb2008, Vol. 18 Issue 4, p1425-1430. 6p. - Publication Year :
- 2008
-
Abstract
- Abstract: A series of OX2R/OX1R dual orexin antagonists was prepared based on a proline bis-amide identified as a screening lead. Through a combination of classical and library synthesis, potency enhancing replacements for both amide portions were discovered. N-methylation of the benzimidazole moiety within the lead structure significantly reduced P-gp susceptibility while increasing potency, giving rise to good brain penetration. A compound from this series has demonstrated in vivo central activity when dosed peripherally in a pharmacodynamic model of orexin activity. [Copyright &y& Elsevier]
- Subjects :
- *OREXINS
*PHARMACODYNAMICS
*NEUROLOGICAL disorders
*PHARMACEUTICAL chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 18
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 29958813
- Full Text :
- https://doi.org/10.1016/j.bmcl.2008.01.001