Novel carbazole derivatives as NPY Y1 antagonists

A series of carbazoles showing antagonist activity at the NPY Y1 receptor were prepared and characterised. Compound 13 combines potent activity with good brain penetration and modest bioavailability. The synthesis of a series of carbazole derivatives and their SAR at the NPY Y1 receptor is described...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-02, Vol.17 (4), p.1043-1046
Main Authors: Leslie, Colin P., Fabio, Romano Di, Bonetti, Francesca, Borriello, Manuela, Braggio, Simone, Forno, Giovanna Dal, Donati, Daniele, Falchi, Alessandro, Ghirlanda, Damiano, Giovannini, Riccardo, Pavone, Francesca, Pecunioso, Angelo, Pentassuglia, Giorgio, Pizzi, Domenica A., Rumboldt, Giovanna, Stasi, Luigi
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biological Availability
Brain - drug effects
Brain - metabolism
Carbazoles - chemical synthesis
Carbazoles - pharmacokinetics
Carbazoles - pharmacology
Chemical Phenomena
Chemistry, Physical
CHO Cells
CNS
Cricetinae
Cricetulus
General and cellular metabolism. Vitamins
Half-Life
Indicators and Reagents
Male
Medical sciences
Neuropeptide Y
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
NPY Y1 antagonist
Obesity
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y - antagonists & inhibitors
Structure-Activity Relationship
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Description
Summary:A series of carbazoles showing antagonist activity at the NPY Y1 receptor were prepared and characterised. Compound 13 combines potent activity with good brain penetration and modest bioavailability. The synthesis of a series of carbazole derivatives and their SAR at the NPY Y1 receptor is described. Modulation of physicochemical properties by appropriate decoration led to the identification of a high-affinity NPY Y1 antagonist that shows high brain penetration and modest oral bioavailability.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.11.034