Novel carbazole derivatives as NPY Y1 antagonists

The synthesis of a series of carbazole derivatives and their SAR at the NPY Y1 receptor is described. Modulation of physicochemical properties by appropriate decoration led to the identification of a high-affinity NPY Y1 antagonist that shows high brain penetration and modest oral bioavailability.

Graphical abstractA series of carbazoles showing antagonist activity at the NPY Y1 receptor were prepared and characterised. Compound 13 combines potent activity with good brain penetration and modest bioavailability.Figure optionsDownload full-size imageDownload as PowerPoint slide