Constrained analogs of CB-1 antagonists: 1,5,6,7-Tetrahydro-4H-pyrrolo[3,2-c]pyridine-4-one derivatives
Pyrrolopyridinones were designed and established as potent constrained analogs of the pyrazole CB-1 receptor antagonist/inverse agonist rimonabant. A representative analog was also demonstrated to cause significant appetite suppression and reduction in body weight gain in rodent models. A series of...
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Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2007-02, Vol.17 (3), p.673-678 |
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Hauptverfasser: | , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Pyrrolopyridinones were designed and established as potent constrained analogs of the pyrazole CB-1 receptor antagonist/inverse agonist rimonabant. A representative analog was also demonstrated to cause significant appetite suppression and reduction in body weight gain in rodent models.
A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazole CB-1 antagonist rimonabant. Certain examples exhibited very potent hCB-1 receptor binding affinity and functional antagonism with
K
i and
K
b values below 10
nM, and with high selectivity for CB-1 over CB-2 (>100-fold). A representative analog was established to cause significant appetite suppression and reduction in body weight gain in industry-standard rat models used to develop new therapeutics for obesity. |
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ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2006.10.095 |