文摘
A novel class of bicyclo[3.1.0]hexanylpiperazine neuropeptide Y (NPY) Y1 antagonists has been designed and synthesized. Scatchard binding analysis showed these compounds to be noncompetitive with [125I]PYY binding to the Y1 receptor. The most potent member, 1-((1伪,3伪,5伪,6尾)-6-(3-ethoxyphenyl)-3-methylbicyclo[3.1.0]hexan-6-yl)-4-phenylpiperazine (2) had an IC50 = 62 nM and displayed excellent oral bioavailability in rat (% F po = 80), as well as good brain penetration (B/P ratio = 0.61). In a spontaneous nocturnal feeding study with male Sprague鈥揇awley rats, 2 significantly reduced food intake during a 12 h period.
Keywords:
bicyclo[3.1.0]hexanylpiperazines; noncompetitive neuropeptide Y Y1 antagonists; brain penetration