Abstract
A series of conformationally constrained bicyclic derivatives derived from SR141716 was prepared and evaluated as hCB(1)-R antagonists and inverse agonists. Optimization of the structure-activity relationships around the 2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one derivative 2a led to the identification of two compounds with oral activity in rodent feeding models (2h and 4a). Replacement of the PP group in 2h with other bicyclic groups resulted in a loss of binding affinity.
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / pharmacology*
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Animals
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Binding Sites
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Bridged Bicyclo Compounds, Heterocyclic / chemistry*
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Feeding Behavior / drug effects*
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Feeding Behavior / physiology
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Models, Biological
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Piperidines / chemistry
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Pyrazoles / chemistry
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Pyrazolones / chemistry
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Pyrimidinones / chemistry
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
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Rimonabant
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Rodentia
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Structure-Activity Relationship
Substances
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Analgesics
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Bridged Bicyclo Compounds, Heterocyclic
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Piperidines
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Pyrazoles
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Pyrazolones
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Pyrimidinones
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Receptor, Cannabinoid, CB1
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pyrazolone
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Rimonabant