Aminopyrazine CB1 receptor inverse agonists

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.

Graphical abstractA series of 5,6-diaryl-2-amino-pyrazines with potent CB1 antagonist-like activity were discovered and shown to have robust effects on food intake in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide