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Constrained analogs of CB-1 antagonists: 1,5,6,7-Tetrahydro-4H-pyrrolo[3,2-c]pyridine-4-one derivatives.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2007 Feb 01; Vol. 17 (3), pp. 673-8. Date of Electronic Publication: 2006 Nov 02. - Publication Year :
- 2007
-
Abstract
- 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 Ki and Kb 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.
- Subjects :
- Animals
Anti-Obesity Agents pharmacokinetics
Body Weight drug effects
Crystallography, X-Ray
Drug Design
Eating drug effects
Humans
Magnetic Resonance Spectroscopy
Male
Models, Molecular
Obesity drug therapy
Pyridones pharmacokinetics
Pyridones pharmacology
Pyrroles pharmacokinetics
Pyrroles pharmacology
Rats
Rats, Wistar
Rats, Zucker
Rimonabant
Structure-Activity Relationship
Weight Gain drug effects
Anti-Obesity Agents chemical synthesis
Anti-Obesity Agents pharmacology
Piperidines chemical synthesis
Piperidines pharmacology
Pyrazoles chemical synthesis
Pyrazoles pharmacology
Pyridones chemical synthesis
Pyrroles chemical synthesis
Receptor, Cannabinoid, CB1 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0960-894X
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 17107792
- Full Text :
- https://doi.org/10.1016/j.bmcl.2006.10.095