New bicyclic cannabinoid receptor-1 (CB1-R) antagonists.

Article Details

Citation

Copy to clipboard

Carpino PA, Griffith DA, Sakya S, Dow RL, Black SC, Hadcock JR, Iredale PA, Scott DO, Fichtner MW, Rose CR, Day R, Dibrino J, Butler M, Debartolo DB, Dutcher D, Gautreau D, Lizano JS, O'connor RE, Sands MA, Kelly-Sullivan D, Ward KM

New bicyclic cannabinoid receptor-1 (CB1-R) antagonists.

Bioorg Med Chem Lett. 2006 Feb;16(3):731-6. Epub 2005 Nov 2.

PubMed ID

16263283 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rimonabant	Cannabinoid receptor 1	Ki (nM)	1	N/A	N/A	Details
Rimonabant	Cannabinoid receptor 1	Ki (nM)	2.1	N/A	N/A	Details