Author/Authors :
David J. Wustrow، نويسنده , , George D. Maynard، نويسنده , , Jun Yuan، نويسنده , , He Zhao، نويسنده , , Jianmin Mao، نويسنده , , Qin Guo، نويسنده , , Mark Kershaw، نويسنده , , Jack Hammer، نويسنده , , Robbin M. Brodbeck، نويسنده , , Kristen E. Near، نويسنده , , Dan Zhou، نويسنده , , David S. Beers، نويسنده , , Bertrand L. Chenard، نويسنده , , James E. Krause، نويسنده , , Alan J. Hutchison، نويسنده ,
Abstract :
A series of 5,6-diaryl-2-amino-pyrazines were prepared and found to have antagonist-like properties at the CB1 receptor. Subsequent SAR studies optimized both receptor potency and drug-like properties including solubility and Cytochrome-P450 inhibition potential. Optimized compounds were demonstrated to be inverse agonists and compared in vivo with rimonabant for their ability to inhibit food intake, to occupy central CB1 receptors and to influence hormonal markers associated with obesity.
Keywords :
Cannabinoid , Rat obesity model , Brain level , CB1 inverse agonist , Ex vivo receptor occupancy
