文摘
A series of novel 2-piperidinopiperidine thiadiazoles were synthesized and evaluated as new leads of histamine H<sub>3sub> receptor antagonists. The 4-(5-([1,4鈥?bipiperidin]-1鈥?yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)morpholine (5u) displayed excellent potency and ex vivo receptor occupancy. Compound 5u was also evaluated in vivo for antidiabetic efficacy in STZ diet-induced obesity type 2 diabetic mice for 2 or 12 days. Non-fasting glucose levels were significantly reduced as compared with vehicle-treated mice. In addition, 5u dose dependently blocked the increase of HbA<sub>1csub> after 12 days of treatment.
Keywords:
Histamine; H<sub>3sub>; antagonist; thiadiazole; type 2 diabetes; non-fasting glucose; HbA<sub>1csub>