Ahmadi A, Khalili M, Farsadrooh M, Ghiasi M, Nahri-Niknafs B
Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran.
Department of Physiology, Neuroscience and Herbal Medicine Research Center, Shahed University, Tehran, Iran.
Drug Res (Stuttg). 2013 Dec;63(12):614-9. doi: 10.1055/s-0033-1349128. Epub 2013 Jul 4.
In this study, new glibenclamide analogues (5a-d) with substituted pharmacological triethoxysilyl propan, allyl and ethoxyphenyl groups for cyclohexyl moiety have been synthesized by condensing sulfonamide (4) with related isocyanate or isothiocyanate's compounds. The newly synthesized drugs were evaluated for their antihyperglycemic and antihyperlipidemic activities with streptozotocin (STZ)-induced diabetic rats. All showed hypoglycemic and hypolipidemic activities compared to the control animals but 5c and 5d exhibited more and significant lowering blood activities similar to glibenclamide. This was concerned with identical affinities to bind with SUR1 receptor. Moreover, the new drugs displayed high efficiency for reducing serum LDL level which resulted in a high HDL/LDL ratio as a good lipid profile compared to other groups.
在本研究中，通过将磺酰胺（4）与相关的异氰酸酯或异硫氰酸酯化合物缩合，合成了具有取代的药理学三乙氧基甲硅烷基丙烷、烯丙基和乙氧基苯基基团的新型格列本脲类似物（5a-d）用于环己基部分。用链脲佐菌素（STZ）诱导的糖尿病大鼠对新合成的药物进行了抗高血糖和抗高血脂活性评估。与对照动物相比，所有药物均显示出降血糖和降血脂活性，但5c和5d表现出更强且显著的降低血液活性，类似于格列本脲。这与它们与SUR1受体结合的相同亲和力有关。此外，与其他组相比，新药在降低血清低密度脂蛋白水平方面表现出高效性，从而产生了良好的脂质谱，即高的高密度脂蛋白/低密度脂蛋白比率。
